VCV001801328.2 - ClinVar

NM_022042.4(SLC26A1):c.824T>C (p.Leu275Pro)

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.

(2)

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.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_022042.4(SLC26A1):c.824T>C (p.Leu275Pro)

Variation ID: 1801328 Accession: VCV001801328.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 4p16.3 4: 990115 (GRCh38) [ NCBI UCSC ] 4: 983903 (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	Dec 3, 2022	May 20, 2023	May 11, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000203.5:c.299+2166A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_022042.4:c.824T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_071325.2:p.Leu275Pro	missense
NM_134425.4:c.576+1013T>C		intron variant
NM_213613.4:c.824T>C	NP_998778.1:p.Leu275Pro	missense
NC_000004.12:g.990115A>G
NC_000004.11:g.983903A>G
NG_008103.1:g.8119A>G
NG_033042.1:g.8322T>C
NG_101697.1:g.443A>G
LRG_1277:g.8119A>G
LRG_1277t1:c.299+2166A>G

... more HGVS ... less HGVS

Protein change

L275P

Other names

Canonical SPDI

NC_000004.12:990114: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.

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

Links

OMIM: 610130.0004 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.
IDUA		-	-	GRCh38 GRCh37	1391	2155
SLC26A1		-	-	GRCh38 GRCh37	3	766

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.
Calcium oxalate urolithiasis	Pathogenic (1)	no assertion criteria provided	Nov 21, 2022	RCV002463389.2
Hypersulfaturia	Pathogenic (1)	no assertion criteria provided	May 11, 2023	RCV003228882.2

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.
Pathogenic (Nov 21, 2022)	no assertion criteria provided Method: clinical testing	Nephrolithiasis susceptibility caused by SLC26A1 (Autosomal recessive inheritance) Affected status: yes Allele origin: inherited	SYNLAB, MVZ Humangenetik Munich Accession: SCV002605235.1 First in ClinVar: Dec 03, 2022 Last updated: Dec 03, 2022	Sex: female
Pathogenic (May 11, 2023)	no assertion criteria provided Method: literature only	HYPERSULFATURIA (1 patient) Affected status: not provided Allele origin: germline	OMIM Accession: SCV003924098.1 First in ClinVar: May 20, 2023 Last updated: May 20, 2023	Publications: PubMed (1) PubMed: 36719378 Comment on evidence: In a 33-year-old woman, born of consanguineous parents, with hypersulfaturia (HYSULF; 620372), Pfau et al. (2023) identified a homozygous c.824T-C transition in the SLC26A1 gene, … (more) In a 33-year-old woman, born of consanguineous parents, with hypersulfaturia (HYSULF; 620372), Pfau et al. (2023) identified a homozygous c.824T-C transition in the SLC26A1 gene, resulting in a leu275-to-pro (L275P) substitution at a highly conserved residue in the fourth transmembrane domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. In vitro functional expression studies in Xenopus oocytes transfected with the mutation showed greatly reduced sulfate and oxalate transport compared to controls. Western blot analysis showed decreased SLC26A1 levels, and immunofluorescent studies showed a marked reduction in cell surface expression of the mutant protein. The findings were consistent with a loss-of-function effect. The patient presented with a 6-year history of intermittent perichondritis of the costovertebral joints that started at the end of her first pregnancy. She had normal kidney function, but a 13-mm stone was found in an upper calyx of the right kidney. Laboratory studies of the patient showed low plasma sulfate with inappropriately high urinary sulfate excretion. Urinary oxalate excretion was normal to only mildly elevated. (less)

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
SLC26A1 is a major determinant of sulfate homeostasis in humans.	Pfau A	The Journal of clinical investigation	2023	PMID: 36719378

Text-mined citations for this variant ...

Record last updated Sep 17, 2024

ClinVar Genomic variation as it relates to human health

NM_022042.4(SLC26A1):c.824T>C (p.Leu275Pro)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...