VCV000137464.24 - ClinVar

NM_024996.7(GFM1):c.476A>G (p.Asn159Ser)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(8)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_024996.7(GFM1):c.476A>G (p.Asn159Ser)

Variation ID: 137464 Accession: VCV000137464.24

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3q25.32 3: 158646851 (GRCh38) [ NCBI UCSC ] 3: 158364640 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jun 23, 2014	Sep 29, 2024	Jan 31, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_024996.7:c.476A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_079272.4:p.Asn159Ser	missense
NM_001308164.2:c.476A>G	NP_001295093.1:p.Asn159Ser	missense
NM_001308166.2:c.476A>G	NP_001295095.1:p.Asn159Ser	missense
NM_001374355.1:c.476A>G	NP_001361284.1:p.Asn159Ser	missense
NM_001374356.1:c.476A>G	NP_001361285.1:p.Asn159Ser	missense
NM_001374357.1:c.251A>G	NP_001361286.1:p.Asn84Ser	missense
NM_001374358.1:c.234+1070A>G		intron variant
NM_001374359.1:c.5+1070A>G		intron variant
NM_001374360.1:c.5+1070A>G		intron variant
NM_001374361.1:c.5+1070A>G		intron variant
NR_164499.1:n.584A>G		non-coding transcript variant
NR_164500.1:n.584A>G		non-coding transcript variant
NR_164502.1:n.584A>G		non-coding transcript variant
NC_000003.12:g.158646851A>G
NC_000003.11:g.158364640A>G
NG_008441.1:g.7324A>G

... more HGVS ... less HGVS

Protein change

N159S, N84S

Other names

p.N159S:AAT>AGT

Canonical SPDI

NC_000003.12:158646850:A:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.01418 (G)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00334

Exome Aggregation Consortium (ExAC) 0.00411

The Genome Aggregation Database (gnomAD) 0.01346

Trans-Omics for Precision Medicine (TOPMed) 0.01405

1000 Genomes Project 0.01418

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01476

1000 Genomes Project 30x 0.01483

Links

ClinGen: CA291061 dbSNP: rs34297061 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
GFM1		-	-	GRCh38 GRCh37	866	918

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign (1)	criteria provided, single submitter	Apr 22, 2013	RCV000125225.1
not provided	Benign (3)	criteria provided, multiple submitters, no conflicts	Jan 31, 2024	RCV000224568.12
Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1	Benign (4)	criteria provided, multiple submitters, no conflicts	Sep 1, 2021	RCV000999807.13

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Jun 12, 2015)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: not provided Allele origin: germline	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics Accession: SCV000280922.1 First in ClinVar: Jun 08, 2016 Last updated: Jun 08, 2016
Benign (Apr 22, 2013)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000168666.10 First in ClinVar: Jun 23, 2014 Last updated: Jun 23, 2014	Comment: This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more) This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
Benign (Apr 05, 2019)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process) Method: clinical testing	Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000885507.2 First in ClinVar: Jun 08, 2016 Last updated: Feb 09, 2020
Benign (Jan 12, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000441853.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (Sep 01, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002795340.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Benign (Jan 31, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001112203.6 First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005304223.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (Sep 16, 2020)	no assertion criteria provided Method: clinical testing	Combined oxidative phosphorylation deficiency 1 Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001456570.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021

Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs34297061 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_024996.7(GFM1):c.476A>G (p.Asn159Ser)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs34297061 ...