Variant chr5-128083972-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000262461.7(SLC12A2):c.18G>C(p.Thr6=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000317 in 1,239,502 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00034 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 5 hom. )

Consequence

SLC12A2
ENST00000262461.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.343

Variant links:

Genes affected

SLC12A2 (HGNC:10911): (solute carrier family 12 member 2) The protein encoded by this gene mediates sodium and chloride transport and reabsorption. The encoded protein is a membrane protein and is important in maintaining proper ionic balance and cell volume. This protein is phosphorylated in response to DNA damage. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

SLC12A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 5-128083972-G-C is Benign according to our data. Variant chr5-128083972-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2146972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A2	NM_001046.3 linkuse as main transcript	c.18G>C	p.Thr6=	synonymous_variant	1/27	ENST00000262461.7	NP_001037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A2	ENST00000262461.7 linkuse as main transcript	c.18G>C	p.Thr6=	synonymous_variant	1/27	1	NM_001046.3	ENSP00000262461	P4	P55011-1
SLC12A2	ENST00000343225.4 linkuse as main transcript	c.18G>C	p.Thr6=	synonymous_variant	1/26	1		ENSP00000340878	A2	P55011-3
SLC12A2	ENST00000509205.5 linkuse as main transcript	c.18G>C	p.Thr6=	synonymous_variant, NMD_transcript_variant	1/27	1		ENSP00000427109
SLC12A2	ENST00000628403.2 linkuse as main transcript	c.18G>C	p.Thr6=	synonymous_variant	1/26	5		ENSP00000486323

Frequencies

GnomAD3 genomes

AF:

0.000337

AC:

AN:

151556

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00952

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000314

AC:

342

AN:

1087840

Hom.:

Cov.:

AF XY:

0.000358

AC XY:

185

AN XY:

517424

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00889

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000823

Gnomad4 OTH exome

AF:

0.000785

GnomAD4 genome

AF:

0.000336

AC:

AN:

151662

Hom.:

Cov.:

AF XY:

0.000513

AC XY:

AN XY:

74120

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00952

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000208

Hom.:

Bravo

AF:

0.0000907

Asia WGS

AF:

0.00360

AC:

AN:

3348

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 26, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	SLC12A2: BP4, BP7 -

SLC12A2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 02, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over