VCV002231313.2 - ClinVar

NM_001077365.2(POMT1):c.141T>G (p.Tyr47Ter)

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.

(1)

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 pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001077365.2(POMT1):c.141T>G (p.Tyr47Ter)

Variation ID: 2231313 Accession: VCV002231313.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 9q34.13 9: 131506132 (GRCh38) [ NCBI UCSC ] 9: 134381519 (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	Feb 8, 2023	May 1, 2024	Jun 8, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NM_001077365.2:c.141T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001070833.1:p.Tyr47Ter	nonsense
NM_001077366.2:c.-22T>G		5 prime UTR
NM_001136113.2:c.141T>G	NP_001129585.1:p.Tyr47Ter	nonsense
NM_001136114.2:c.-122-271T>G		intron variant
NM_001353193.2:c.141T>G	NP_001340122.2:p.Tyr47Ter	nonsense
NM_001353194.2:c.-22T>G		5 prime UTR
NM_001353195.2:c.-122-271T>G		intron variant
NM_001353196.2:c.123-271T>G		intron variant
NM_001353197.2:c.-22T>G		5 prime UTR
NM_001353198.2:c.-22T>G		5 prime UTR
NM_001353199.2:c.-122-271T>G		intron variant
NM_001353200.2:c.-80-271T>G		intron variant
NM_001374689.1:c.-22T>G		5 prime UTR
NM_001374690.1:c.141T>G	NP_001361619.1:p.Tyr47Ter	nonsense
NM_001374691.1:c.-71-1236T>G		intron variant
NM_001374692.1:c.-71-1236T>G		intron variant
NM_001374693.1:c.-22T>G		5 prime UTR
NM_001374695.1:c.-30+1792T>G		intron variant
NM_007171.4:c.141T>G	NP_009102.4:p.Tyr47Ter	nonsense
NR_148391.2:n.175T>G		non-coding transcript variant
NR_148392.2:n.327T>G		non-coding transcript variant
NR_148393.2:n.175T>G		non-coding transcript variant
NR_148394.2:n.175T>G		non-coding transcript variant
NR_148395.2:n.327T>G		non-coding transcript variant
NR_148398.2:n.175T>G		non-coding transcript variant
NR_148399.2:n.567T>G		non-coding transcript variant
NC_000009.12:g.131506132T>G
NC_000009.11:g.134381519T>G
NG_008896.2:g.8231T>G
LRG_842:g.8231T>G
LRG_842t1:c.141T>G	LRG_842p1:p.Tyr47Ter
LRG_842t2:c.141T>G	LRG_842p2:p.Tyr47Ter

... more HGVS ... less HGVS

Protein change

Y47*

Other names

Canonical SPDI

NC_000009.12:131506131:T: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.

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

Links

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.
POMT1		-	-	GRCh38 GRCh37	1162	1203

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.
Inborn genetic diseases	Likely pathogenic (1)	criteria provided, single submitter	Jun 8, 2021	RCV002707991.2

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 pathogenic (Jun 08, 2021)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV003556183.2 First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024	Publications: PubMed (3) PubMed: 25954003‚ 27618451‚ 28490743 Comment: The c.141T>G (p.Y47) alteration, located in exon 3 (coding exon 2) of the POMT1 gene, consists of a T to G substitution at nucleotide position … (more) The c.141T>G (p.Y47) alteration, located in exon 3 (coding exon 2) of the POMT1 gene, consists of a T to G substitution at nucleotide position 141. This changes the amino acid from a tyrosine (Y) to a stop codon at amino acid position 47. The predicted stop codon occurs in the 5' end of the POMT1 gene. Premature termination codons in the 5’ end of a gene have been reported to escape nonsense-mediated mRNA decay and/or lead to re-initiation (Rivas, 2015; Lindeboom, 2016; Rhee, 2017). Direct evidence for this alteration is unavailable, however premature termination codons are typically deleterious in nature. Based on data from the Genome Aggregation Database (gnomAD), the POMT1 c.141T>G alteration was not observed, with coverage at this position. Based on the available evidence, this alteration is classified as likely pathogenic. (less)

Comment:

The c.141T>G (p.Y47*) alteration, located in exon 3 (coding exon 2) of the POMT1 gene, consists of a T to G substitution at nucleotide position 141. This changes the amino acid from a tyrosine (Y) to a stop codon at amino acid position 47. The predicted stop codon occurs in the 5' end of the POMT1 gene. Premature termination codons in the 5’ end of a gene have been reported to escape nonsense-mediated mRNA decay and/or lead to re-initiation (Rivas, 2015; Lindeboom, 2016; Rhee, 2017). Direct evidence for this alteration is unavailable, however premature termination codons are typically deleterious in nature. Based on data from the Genome Aggregation Database (gnomAD), the POMT1 c.141T>G alteration was not observed, with coverage at this position. Based on the available evidence, this alteration is classified as likely pathogenic.

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

Title	Author	Journal	Year	Link
Allelic imbalance of somatic mutations in cancer genomes and transcriptomes.	Rhee JK	Scientific reports	2017	PMID: 28490743
The rules and impact of nonsense-mediated mRNA decay in human cancers.	Lindeboom RG	Nature genetics	2016	PMID: 27618451
Human genomics. Effect of predicted protein-truncating genetic variants on the human transcriptome.	Rivas MA	Science (New York, N.Y.)	2015	PMID: 25954003

Text-mined citations for this variant ...

Record last updated May 01, 2024

ClinVar Genomic variation as it relates to human health

NM_001077365.2(POMT1):c.141T>G (p.Tyr47Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...