5-128084110-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001046.3(SLC12A2):c.156C>G(p.Asp52Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,310,550 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D52N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 12 hom. )

Consequence

SLC12A2
NM_001046.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.63

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023020804).

BP6

Variant 5-128084110-C-G is Benign according to our data. Variant chr5-128084110-C-G is described in ClinVar as [Benign]. Clinvar id is 1599916.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A2	NM_001046.3 linkuse as main transcript	c.156C>G	p.Asp52Glu	missense_variant	1/27	ENST00000262461.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A2	ENST00000262461.7 linkuse as main transcript	c.156C>G	p.Asp52Glu	missense_variant	1/27	1	NM_001046.3	P4	P55011-1
SLC12A2	ENST00000343225.4 linkuse as main transcript	c.156C>G	p.Asp52Glu	missense_variant	1/26	1		A2	P55011-3
SLC12A2	ENST00000509205.5 linkuse as main transcript	c.156C>G	p.Asp52Glu	missense_variant, NMD_transcript_variant	1/27	1
SLC12A2	ENST00000628403.2 linkuse as main transcript	c.156C>G	p.Asp52Glu	missense_variant	1/26	5

Frequencies

GnomAD3 genomes

AF:

0.00117

AC:

177

AN:

151596

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000885

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00513

AC:

AN:

18730

Hom.:

AF XY:

0.00691

AC XY:

AN XY:

11292

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000597

Gnomad ASJ exome

AF:

0.00315

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0180

Gnomad FIN exome

AF:

0.000705

Gnomad NFE exome

AF:

0.00157

Gnomad OTH exome

AF:

0.00172

GnomAD4 exome

AF:

0.00134

AC:

1557

AN:

1158846

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

883

AN XY:

563498

show subpopulations

Gnomad4 AFR exome

AF:

0.000212

Gnomad4 AMR exome

AF:

0.000496

Gnomad4 ASJ exome

AF:

0.00384

Gnomad4 EAS exome

AF:

0.000115

Gnomad4 SAS exome

AF:

0.0146

Gnomad4 FIN exome

AF:

0.0000791

Gnomad4 NFE exome

AF:

0.000814

Gnomad4 OTH exome

AF:

0.00201

GnomAD4 genome

AF:

0.00117

AC:

178

AN:

151704

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

106

AN XY:

74152

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.00289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0149

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000885

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000953

Hom.:

Bravo

AF:

0.000933

ExAC

AF:

0.00412

AC:

Asia WGS

AF:

0.00815

AC:

AN:

3328

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

Cadd

Benign

3.9

Dann

Benign

0.66

DEOGEN2

Benign

0.17

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.63

T;T;T

MetaRNN

Benign

0.0023

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.69

N;.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.060

N;.;N

REVEL

Benign

0.23

Sift

Benign

1.0

T;.;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0010

B;.;B

Vest4

0.049

MutPred

0.070

Gain of methylation at R57 (P = 0.1338);Gain of methylation at R57 (P = 0.1338);Gain of methylation at R57 (P = 0.1338);

MVP

0.34

MPC

0.65

ClinPred

0.0090

GERP RS

0.62

Varity_R

0.037

gMVP

0.18

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