NM_001126108.2(SLC12A3):c.2633+2T>A AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 14, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003558301.2

Allele description [Variation Report for NM_001126108.2(SLC12A3):c.2633+2T>A]

NM_001126108.2(SLC12A3):c.2633+2T>A

Gene:

SLC12A3:solute carrier family 12 member 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q13

Genomic location:

Preferred name:

NM_001126108.2(SLC12A3):c.2633+2T>A

HGVS:

NC_000016.10:g.56894644T>A
NG_009386.2:g.34438T>A
NM_000339.3:c.2660+2T>A
NM_001126107.2:c.2657+2T>A
NM_001126108.2:c.2633+2T>AMANE SELECT
NM_001410896.1:c.2630+2T>A
NC_000016.9:g.56928556T>A

Molecular consequence:

NM_000339.3:c.2660+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001126107.2:c.2657+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001126108.2:c.2633+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001410896.1:c.2630+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004309458	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 14, 2023)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 16199547, 20848653, 22009145, 25841442, 22679066, 24830959, 29403282, 30413979, 30596175, 31672324, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004309458

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 14, 2023)

germline

clinical testing

PubMed (11)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Generation and analysis of the thiazide-sensitive Na+ -Cl- cotransporter (Ncc/Slc12a3) Ser707X knockin mouse as a model of Gitelman syndrome.

Yang SS, Lo YF, Yu IS, Lin SW, Chang TH, Hsu YJ, Chao TK, Sytwu HK, Uchida S, Sasaki S, Lin SH.

Hum Mutat. 2010 Dec;31(12):1304-15. doi: 10.1002/humu.21364. Epub 2010 Oct 14.

PubMed [citation]

PMID:: 20848653

See all PubMed Citations (11)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004309458.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

This sequence change affects a donor splice site in intron 22 of the SLC12A3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SLC12A3 are known to be pathogenic (PMID: 20848653, 22009145, 25841442). This variant is present in population databases (no rsID available, gnomAD 0.002%). Disruption of this splice site has been observed in individual(s) with Gitelman syndrome (PMID: 22679066, 24830959, 29403282, 30413979, 30596175, 31672324). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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