rs4726

Positions:

• chr11-62885307-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001013251.3(SLC3A2):​c.949C>T​(p.Leu317=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,614,036 control chromosomes in the GnomAD database, including 39,717 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2698 hom., cov: 31)
  • Exomes 𝑓: 0.22 (37019 hom.)
• Consequence: SLC3A2 NM_001013251.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.503

Genes affected

SLC3A2 (HGNC:11026): (solute carrier family 3 member 2) This gene is a member of the solute carrier family and encodes a cell surface, transmembrane protein. The protein exists as the heavy chain of a heterodimer, covalently bound through di-sulfide bonds to one of several possible light chains. The encoded transporter plays a role in regulation of intracellular calcium levels and transports L-type amino acids. Alternatively spliced transcript variants, encoding different isoforms, have been characterized. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-0.503 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC3A2	NM_001013251.3	c.949C>T	p.Leu317=	synonymous_variant	6/9	ENST00000338663.12	NP_001013269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC3A2	ENST00000338663.12	c.949C>T	p.Leu317=	synonymous_variant	6/9	1	NM_001013251.3	ENSP00000340815	P2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25326 AN: 152102 Hom.: 2698 Cov.: 31

Gnomad AFR AF: 0.0464

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.0817

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.184

GnomAD3 exomes AF: 0.180 AC: 45287 AN: 251436 Hom.: 4776 AF XY: 0.182 AC XY: 24722 AN XY: 135894

Gnomad AFR exome AF: 0.0418

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.211

Gnomad EAS exome AF: 0.199

Gnomad SAS exome AF: 0.0798

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.235

Gnomad OTH exome AF: 0.204

GnomAD4 exome AF: 0.217 AC: 317911 AN: 1461816 Hom.: 37019 Cov.: 34 AF XY: 0.214 AC XY: 155369 AN XY: 727224

Gnomad4 AFR exome AF: 0.0367

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.213

Gnomad4 EAS exome AF: 0.188

Gnomad4 SAS exome AF: 0.0844

Gnomad4 FIN exome AF: 0.215

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.166 AC: 25314 AN: 152220 Hom.: 2698 Cov.: 31 AF XY: 0.163 AC XY: 12162 AN XY: 74422

Gnomad4 AFR AF: 0.0463

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.0824

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.181

Alfa AF: 0.217 Hom.: 6319

Bravo AF: 0.160

Asia WGS AF: 0.119 AC: 414 AN: 3478

EpiCase AF: 0.234

EpiControl AF: 0.237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.5
DANN	Benign	0.85

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: rs4726; hg19: chr11-62652779; COSMIC: COSV58602939; COSMIC: COSV58602939;