5-128084101-G-C

Position:

• chr5-128084101-G-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001046.3(SLC12A2):​c.147G>C​(p.Ala49=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,313,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A49A) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: SLC12A2 NM_001046.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-128084101-G-C is Benign according to our data. Variant chr5-128084101-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2153995.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.64 with no splicing effect.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000923 AC: 14 AN: 151648 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000722

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000959

GnomAD4 exome AF: 0.0000121 AC: 14 AN: 1161784 Hom.: 0 Cov.: 30 AF XY: 0.00000708 AC XY: 4 AN XY: 565216

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000243

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000786

Gnomad4 NFE exome AF: 0.00000620

Gnomad4 OTH exome AF: 0.0000646

GnomAD4 genome AF: 0.0000923 AC: 14 AN: 151756 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74176

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000721

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000949

Bravo AF: 0.000136

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 18, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.8
DANN	Benign	0.64
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;