Variant 5-128134167-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001046.3(SLC12A2):c.1191A>G(p.Glu397Glu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,498,932 control chromosomes in the GnomAD database, including 52,196 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 11677 hom., cov: 32)

Exomes 𝑓: 0.23 ( 40519 hom. )

Consequence

SLC12A2
NM_001046.3 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0110

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 5-128134167-A-G is Benign according to our data. Variant chr5-128134167-A-G is described in ClinVar as [Benign]. Clinvar id is 1262133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.011 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A2	NM_001046.3 link	c.1191A>G	p.Glu397Glu	splice_region_variant, synonymous_variant	6/27	ENST00000262461.7	NP_001037.1	P55011-1Q53ZR1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC12A2	ENST00000262461.7 link	c.1191A>G	p.Glu397Glu	splice_region_variant, synonymous_variant	6/27	1	NM_001046.3	ENSP00000262461.2	P55011-1
SLC12A2	ENST00000343225.4 link	c.1191A>G	p.Glu397Glu	splice_region_variant, synonymous_variant	6/26	1		ENSP00000340878.4	P55011-3
SLC12A2	ENST00000509205.5 link	n.1191A>G		splice_region_variant, non_coding_transcript_exon_variant	6/27	1		ENSP00000427109.1	G3XAL9
SLC12A2	ENST00000628403.2 link	c.1191A>G	p.Glu397Glu	splice_region_variant, synonymous_variant	6/26	5		ENSP00000486323.1	G3XAL9

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

52400

AN:

151734

Hom.:

11641

Cov.:

show subpopulations

Gnomad AFR

AF:

0.631

Gnomad AMI

AF:

0.219

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.255

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.304

GnomAD3 exomes

AF:

0.278

AC:

69070

AN:

248184

Hom.:

11552

AF XY:

0.262

AC XY:

35155

AN XY:

134142

show subpopulations

Gnomad AFR exome

AF:

0.642

Gnomad AMR exome

AF:

0.406

Gnomad ASJ exome

AF:

0.264

Gnomad EAS exome

AF:

0.331

Gnomad SAS exome

AF:

0.211

Gnomad FIN exome

AF:

0.212

Gnomad NFE exome

AF:

0.213

Gnomad OTH exome

AF:

0.242

GnomAD4 exome

AF:

0.231

AC:

311594

AN:

1347080

Hom.:

40519

Cov.:

AF XY:

0.229

AC XY:

154554

AN XY:

676250

show subpopulations

Gnomad4 AFR exome

AF:

0.639

Gnomad4 AMR exome

AF:

0.400

Gnomad4 ASJ exome

AF:

0.269

Gnomad4 EAS exome

AF:

0.352

Gnomad4 SAS exome

AF:

0.213

Gnomad4 FIN exome

AF:

0.217

Gnomad4 NFE exome

AF:

0.208

Gnomad4 OTH exome

AF:

0.243

GnomAD4 genome

AF:

0.346

AC:

52492

AN:

151852

Hom.:

11677

Cov.:

AF XY:

0.345

AC XY:

25586

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.631

Gnomad4 AMR

AF:

0.347

Gnomad4 ASJ

AF:

0.260

Gnomad4 EAS

AF:

0.334

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.210

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.306

Alfa

AF:

0.255

Hom.:

5044

Bravo

AF:

0.371

Asia WGS

AF:

0.339

AC:

1177

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Feb 03, 2025	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

9.0

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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