VCV000646707.9 - ClinVar

NM_001164277.2(SLC37A4):c.1287_1290del (p.Ter430GluextTer?)

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.

(4)

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.

Conflicting classifications of pathogenicity
Pathogenic(2); Likely pathogenic(1); Uncertain significance(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001164277.2(SLC37A4):c.1287_1290del (p.Ter430GluextTer?)

Variation ID: 646707 Accession: VCV000646707.9

Type and length

Deletion, 4 bp

Location

Cytogenetic: 11q23.3 11: 119024910-119024913 (GRCh38) [ NCBI UCSC ] 11: 118895620-118895623 (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	Aug 14, 2019	Sep 1, 2024	Feb 14, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001164277.2:c.1287_1290del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001157749.1:p.Ter430GluextTer?	frameshift
NM_001164277.1:c.1287_1290delGTGA
NM_001164278.2:c.1353_1356del	NP_001157750.1:p.Ter452GluextTer?	frameshift
NM_001164279.2:c.1068_1071del	NP_001157751.1:p.Ter357GluextTer?	frameshift
NM_001164280.2:c.1287_1290del	NP_001157752.1:p.Ter430GluextTer?	frameshift
NM_001467.6:c.1287_1290del	NP_001458.1:p.Ter430GluextTer?	frameshift
NC_000011.10:g.119024913_119024916del
NC_000011.9:g.118895623_118895626del
NG_013331.1:g.10993_10996del
LRG_187:g.10993_10996del

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000011.10:119024909:TCACTCA:TCA

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

dbSNP: rs1592107594 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.
SLC37A4		-	-	GRCh38 GRCh38 GRCh37	1010	1051

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.
Glucose-6-phosphate transport defect	Conflicting interpretations of pathogenicity (4)	criteria provided, conflicting classifications	Feb 14, 2023	RCV000801048.12

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.
Pathogenic (Jul 22, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Glucose-6-phosphate transport defect (Autosomal recessive inheritance) Affected status: yes Allele origin: inherited	Centre for Human Genetics Accession: SCV001482277.1 First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021	Comment: disease causing Number of individuals with the variant: 1 Clinical Features: neutropenia (present) , neutrophil dysfunction (present) Ethnicity/Population group: Indian Geographic origin: India Secondary finding: no
Uncertain significance (Aug 13, 2021)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Glucose-6-phosphate transport defect Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000940804.2 First in ClinVar: Aug 14, 2019 Last updated: May 16, 2022
Likely pathogenic (Feb 14, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Glucose-6-phosphate transport defect (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Neuberg Centre For Genomic Medicine, NCGM Accession: SCV004176529.1 First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023	Comment: The frameshift c.1287_1290del(p.Ter430GlufsTer53) variant in SLC37A4 gene has been reported previously in heterozygous state in an individual affected with glycogen storage disorders (Kumar TV, et. … (more) The frameshift c.1287_1290del(p.Ter430GlufsTer53) variant in SLC37A4 gene has been reported previously in heterozygous state in an individual affected with glycogen storage disorders (Kumar TV, et. al., 2022). The p.Ter430GlufsTer53 variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance/ Pathogenic. Due to frameshift change, the sequence of a stop codon is changed to specify an amino acid Glutamic Acid instead and translation will continue until another stop codon is found at position Ter53. Loss of function variants have been previously reported to be disease causing. However since this variant is present in the last exon, functional studies will be required to prove protein truncation. Hence the variant is classified as Likely Pathogenic. (less) Clinical Features: Abnormal metabolism (present)
Pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Glucose-6-phosphate transport defect (Autosomal recessive inheritance) Affected status: yes Allele origin: biparental	Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India Accession: SCV004015018.2 First in ClinVar: Jul 22, 2023 Last updated: Sep 01, 2024	Publications: DOI: 10.1371/journal.pone.0270373 DOI: 10.1371/journal.pone.0270373 Sex: male

Comment:

The frameshift c.1287_1290del(p.Ter430GlufsTer53) variant in SLC37A4 gene has been reported previously in heterozygous state in an individual affected with glycogen storage disorders (Kumar TV, et. al., 2022). The p.Ter430GlufsTer53 variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance/ Pathogenic. Due to frameshift change, the sequence of a stop codon is changed to specify an amino acid Glutamic Acid instead and translation will continue until another stop codon is found at position Ter53. Loss of function variants have been previously reported to be disease causing. However since this variant is present in the last exon, functional studies will be required to prove protein truncation. Hence the variant 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
Molecular and clinical profiling in a large cohort of Asian Indians with glycogen storage disorders.	Kumar TV	PloS one	2022	DOI: 10.1371/journal.pone.0270373

Text-mined citations for rs1592107594 ...

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_001164277.2(SLC37A4):c.1287_1290del (p.Ter430GluextTer?)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1592107594 ...