VCV000414873.26 - ClinVar

NM_001370298.3(FGD4):c.647C>T (p.Thr216Ile)

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.

Likely 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_001370298.3(FGD4):c.647C>T (p.Thr216Ile)

Variation ID: 414873 Accession: VCV000414873.26

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 12p11.21 12: 32582103 (GRCh38) [ NCBI UCSC ] 12: 32735037 (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	Apr 17, 2017	Oct 8, 2024	Dec 4, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001370298.3:c.647C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001357227.2:p.Thr216Ile	missense
NM_001304481.2:c.491C>T	NP_001291410.1:p.Thr164Ile	missense
NM_001304483.2:c.-609C>T		5 prime UTR
NM_001304484.2:c.-916C>T		5 prime UTR
NM_001330373.2:c.-44C>T		5 prime UTR
NM_001330374.2:c.-44C>T		5 prime UTR
NM_001370297.1:c.49-16394C>T		intron variant
NM_001384126.1:c.647C>T	NP_001371055.1:p.Thr216Ile	missense
NM_001384127.1:c.236C>T	NP_001371056.1:p.Thr79Ile	missense
NM_001384128.1:c.236C>T	NP_001371057.1:p.Thr79Ile	missense
NM_001384130.1:c.-44C>T		5 prime UTR
NM_001384131.1:c.236C>T	NP_001371060.1:p.Thr79Ile	missense
NM_001384132.1:c.236C>T	NP_001371061.1:p.Thr79Ile	missense
NM_001385118.1:c.236C>T	NP_001372047.1:p.Thr79Ile	missense
NM_139241.3:c.236C>T	NP_640334.2:p.Thr79Ile	missense
NR_168884.1:n.473C>T		non-coding transcript variant
NC_000012.12:g.32582103C>T
NC_000012.11:g.32735037C>T
NG_008626.2:g.187575C>T
LRG_240:g.187575C>T
LRG_240t1:c.236C>T	LRG_240p1:p.Thr79Ile
LRG_240t2:c.491C>T	LRG_240p2:p.Thr164Ile

... more HGVS ... less HGVS

Protein change

T79I, T164I, T216I

Other names

Canonical SPDI

NC_000012.12:32582102:C:T

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.

0.00300 (T)

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

The Genome Aggregation Database (gnomAD), exomes 0.00071

Exome Aggregation Consortium (ExAC) 0.00078

The Genome Aggregation Database (gnomAD) 0.00213

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00238

Trans-Omics for Precision Medicine (TOPMed) 0.00264

1000 Genomes Project 30x 0.00297

1000 Genomes Project 0.00300

Links

ClinGen: CA6506604 dbSNP: rs145115430 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.
FGD4		-	-	GRCh38 GRCh37	745	785

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 provided	Likely benign (3)	criteria provided, multiple submitters, no conflicts	Apr 26, 2021	RCV000757290.9
Charcot-Marie-Tooth disease type 4	Likely benign (1)	criteria provided, single submitter	Dec 4, 2023	RCV001079716.8
Charcot-Marie-Tooth disease	Likely benign (1)	criteria provided, single submitter	-	RCV001173489.1
Charcot-Marie-Tooth disease type 4H	Likely benign (1)	criteria provided, single submitter	Sep 22, 2023	RCV001283349.9
Inborn genetic diseases	Likely benign (1)	criteria provided, single submitter	Sep 10, 2019	RCV002446876.2
FGD4-related disorder	Likely benign (1)	no assertion criteria provided	Dec 3, 2019	RCV003960079.2

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.
Likely benign (Nov 09, 2018)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Athena Diagnostics Accession: SCV001143906.1 First in ClinVar: Jan 18, 2020 Last updated: Jan 18, 2020
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Charcot-Marie-Tooth disease Affected status: yes Allele origin: germline	Molecular Genetics Laboratory, London Health Sciences Centre Accession: SCV001336578.1 First in ClinVar: Jun 14, 2020 Last updated: Jun 14, 2020
Likely benign (Apr 26, 2021)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001771086.1 First in ClinVar: Aug 07, 2021 Last updated: Aug 07, 2021
Likely benign (Dec 04, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Charcot-Marie-Tooth disease type 4 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000558951.8 First in ClinVar: Apr 17, 2017 Last updated: Feb 14, 2024
Likely benign (Sep 22, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	Charcot-Marie-Tooth disease type 4H Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000885450.3 First in ClinVar: Feb 18, 2019 Last updated: Feb 20, 2024
Likely benign (Sep 10, 2019)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002735016.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Comment: This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more) This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Likely 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: SCV005216561.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Likely benign (Dec 03, 2019)	no assertion criteria provided Method: clinical testing	FGD4-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004772296.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Comment:

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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 rs145115430 ...

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 Oct 13, 2024

ClinVar Genomic variation as it relates to human health

NM_001370298.3(FGD4):c.647C>T (p.Thr216Ile)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs145115430 ...