5-128084101-G-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001046.3(SLC12A2):c.147G>T(p.Ala49=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000779 in 1,313,538 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 Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A49A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0039 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (2 hom.)
• Consequence: SLC12A2 NM_001046.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.64

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 5-128084101-G-T is Benign according to our data. Variant chr5-128084101-G-T is described in ClinVar as [Benign]. Clinvar id is 1638143.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.64 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A2	NM_001046.3	c.147G>T	p.Ala49=	synonymous_variant	1/27	ENST00000262461.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A2	ENST00000262461.7	c.147G>T	p.Ala49=	synonymous_variant	1/27	1	NM_001046.3	P4
SLC12A2	ENST00000343225.4	c.147G>T	p.Ala49=	synonymous_variant	1/26	1		A2
SLC12A2	ENST00000509205.5	c.147G>T	p.Ala49=	synonymous_variant, NMD_transcript_variant	1/27	1
SLC12A2	ENST00000628403.2	c.147G>T	p.Ala49=	synonymous_variant	1/26	5

Frequencies

GnomAD3 genomes AF: 0.00388 AC: 588 AN: 151648 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000382 AC: 8 AN: 20916 Hom.: 0 AF XY: 0.000395 AC XY: 5 AN XY: 12644

Gnomad AFR exome AF: 0.0126

Gnomad AMR exome AF: 0.000558

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00152

GnomAD4 exome AF: 0.000373 AC: 433 AN: 1161782 Hom.: 2 Cov.: 30 AF XY: 0.000350 AC XY: 198 AN XY: 565216

Gnomad4 AFR exome AF: 0.0151

Gnomad4 AMR exome AF: 0.000729

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000227

Gnomad4 OTH exome AF: 0.000947

GnomAD4 genome AF: 0.00389 AC: 590 AN: 151756 Hom.: 4 Cov.: 32 AF XY: 0.00368 AC XY: 273 AN XY: 74176

Gnomad4 AFR AF: 0.0137

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.0000698 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 18, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2023	SLC12A2: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	5.7
Dann	Benign	0.76
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

Other links and lift over

dbSNP: rs555325149; hg19: chr5-127419793;