VCV000790165.13 - ClinVar

NM_001126108.2(SLC12A3):c.966G>A (p.Ala322=)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Uncertain significance (1); Benign (1)

2 out of 3 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001126108.2(SLC12A3):c.966G>A (p.Ala322=)

Variation ID: 790165 Accession: VCV000790165.13

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 16q13 16: 56872657 (GRCh38) [ NCBI UCSC ] 16: 56906569 (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 17, 2019	Mar 7, 2026	Sep 14, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001126108.2:c.966G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001119580.2:p.Ala322=	synonymous
NM_000339.3:c.966G>A	NP_000330.3:p.Ala322=	synonymous
NM_001126107.2:c.963G>A	NP_001119579.2:p.Ala321=	synonymous
NC_000016.10:g.56872657G>A
NC_000016.9:g.56906569G>A
NG_009386.2:g.12451G>A

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000016.10:56872656:G:A

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.

0.00020 (A)

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

1000 Genomes Project 30x 0.00016

1000 Genomes Project 0.00020

Exome Aggregation Consortium (ExAC) 0.00021

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00054

The Genome Aggregation Database (gnomAD) 0.00072

The Genome Aggregation Database (gnomAD) 0.00063

Trans-Omics for Precision Medicine (TOPMed) 0.00082

The Genome Aggregation Database (gnomAD), exomes 0.00017

Links

ClinGen: CA8069292 dbSNP: rs149172580 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.
SLC12A3		Gene associated with autosomal recessive phenotype	No evidence available	GRCh38 GRCh37	1987	2098

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	Benign (1)	criteria provided, single submitter	Sep 14, 2025	RCV000972904.11
Familial hypokalemia-hypomagnesemia	Uncertain significance (1)	no assertion criteria provided	Mar 10, 2020	RCV001274423.1
not specified	Uncertain significance (1)	criteria provided, single submitter	Sep 18, 2024	RCV004782616.1

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.	Expand all rows Collapse all rows 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.
Uncertain significance (Sep 18, 2024) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	not specified	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV005395465.1 First in ClinVar: Nov 17, 2024 Last updated: Nov 17, 2024	Comment: show Variant summary: SLC12A3 c.966G>A (p.Ala322Ala) alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Two predict the variant weakens a 3' acceptor site. Three predict the variant creates a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00017 in 251446 control chromosomes, predominantly at a frequency of 0.0021 within the African or African-American subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in SLC12A3 causing Familial Hypokalemia-Hypomagnesemia, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.966G>A in individuals affected with Familial Hypokalemia-Hypomagnesemia and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 790165). Based on the evidence outlined above, the variant was classified as uncertain significance. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Sep 14, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001120634.8 First in ClinVar: Dec 17, 2019 Last updated: Mar 07, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Mar 10, 2020) N Not contributing to aggregate classification	no assertion criteria provided	Gitelman syndrome	Natera, Inc. Accession: SCV001458554.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

Variant summary: SLC12A3 c.966G>A (p.Ala322Ala) alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Two predict the variant weakens a 3' acceptor site. Three predict the variant creates a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00017 in 251446 control chromosomes, predominantly at a frequency of 0.0021 within the African or African-American subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in SLC12A3 causing Familial Hypokalemia-Hypomagnesemia, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.966G>A in individuals affected with Familial Hypokalemia-Hypomagnesemia and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 790165). Based on the evidence outlined above, the variant was classified as uncertain significance.

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 rs149172580 ...

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 Jun 14, 2026