Variant chr5-128084056-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001046.3(SLC12A2):c.102G>A(p.Leu34=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 1,302,660 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 13 hom. )

Consequence

SLC12A2
NM_001046.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.513

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 5-128084056-G-A is Benign according to our data. Variant chr5-128084056-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1659746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.513 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 13 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A2	NM_001046.3 linkuse as main transcript	c.102G>A	p.Leu34=	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.102G>A	p.Leu34=	synonymous_variant	1/27	1	NM_001046.3	ENSP00000262461	P4	P55011-1
SLC12A2	ENST00000343225.4 linkuse as main transcript	c.102G>A	p.Leu34=	synonymous_variant	1/26	1		ENSP00000340878	A2	P55011-3
SLC12A2	ENST00000509205.5 linkuse as main transcript	c.102G>A	p.Leu34=	synonymous_variant, NMD_transcript_variant	1/27	1		ENSP00000427109
SLC12A2	ENST00000628403.2 linkuse as main transcript	c.102G>A	p.Leu34=	synonymous_variant	1/26	5		ENSP00000486323

Frequencies

GnomAD3 genomes

AF:

0.00242

AC:

367

AN:

151766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000773

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00354

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000192

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00401

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00139

AC:

AN:

14338

Hom.:

AF XY:

0.00102

AC XY:

AN XY:

8800

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.000812

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00251

Gnomad OTH exome

AF:

0.00207

GnomAD4 exome

AF:

0.00391

AC:

4501

AN:

1150786

Hom.:

Cov.:

AF XY:

0.00397

AC XY:

2217

AN XY:

557960

show subpopulations

Gnomad4 AFR exome

AF:

0.000515

Gnomad4 AMR exome

AF:

0.00298

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000102

Gnomad4 FIN exome

AF:

0.000119

Gnomad4 NFE exome

AF:

0.00442

Gnomad4 OTH exome

AF:

0.00411

GnomAD4 genome

AF:

0.00242

AC:

367

AN:

151874

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

156

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00354

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000192

Gnomad4 NFE

AF:

0.00401

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.00254

Hom.:

Bravo

AF:

0.00287

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 11, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	SLC12A2: BP4, BP7 -

Kilquist syndrome;C5436768:Hearing loss, autosomal dominant 78;C5436771:Delpire-McNeill syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.1

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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