5-128084053-A-G

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.99A>G(p.Glu33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000624 in 1,298,470 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: SLC12A2 NM_001046.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0170

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 5-128084053-A-G is Benign according to our data. Variant chr5-128084053-A-G is described in ClinVar as [Benign]. Clinvar id is 2051934.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.017 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A2	NM_001046.3	c.99A>G	p.Glu33=	synonymous_variant	1/27	ENST00000262461.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A2	ENST00000262461.7	c.99A>G	p.Glu33=	synonymous_variant	1/27	1	NM_001046.3	P4
SLC12A2	ENST00000343225.4	c.99A>G	p.Glu33=	synonymous_variant	1/26	1		A2
SLC12A2	ENST00000509205.5	c.99A>G	p.Glu33=	synonymous_variant, NMD_transcript_variant	1/27	1
SLC12A2	ENST00000628403.2	c.99A>G	p.Glu33=	synonymous_variant	1/26	5

Frequencies

GnomAD3 genomes AF: 0.000356 AC: 54 AN: 151582 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000235 AC: 27 AN: 1146780 Hom.: 0 Cov.: 30 AF XY: 0.0000234 AC XY: 13 AN XY: 555556

Gnomad4 AFR exome AF: 0.000945

Gnomad4 AMR exome AF: 0.0000953

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000262

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000104

Gnomad4 OTH exome AF: 0.0000437

GnomAD4 genome AF: 0.000356 AC: 54 AN: 151690 Hom.: 0 Cov.: 32 AF XY: 0.000458 AC XY: 34 AN XY: 74160

Gnomad4 AFR AF: 0.00128

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000498 Hom.: 0

Bravo AF: 0.000400

Asia WGS AF: 0.000293 AC: 1 AN: 3432

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 16, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.9
Dann	Benign	0.71
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: rs569634871; hg19: chr5-127419745;