rs4726

Variant names:

• chr11-62885307-C-T
• rs4726
• NM_001013251.3:c.949C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001013251.3(SLC3A2):​c.949C>T​(p.Leu317Leu) 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
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.01).
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013251.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC3A2	NM_001013251.3	MANE Select	c.949C>T	p.Leu317Leu	synonymous	Exon 6 of 9	NP_001013269.1	P08195-2
	SLC3A2	NM_001012662.3		c.1255C>T	p.Leu419Leu	synonymous	Exon 9 of 12	NP_001012680.1	P08195-5
	SLC3A2	NM_002394.6		c.1252C>T	p.Leu418Leu	synonymous	Exon 9 of 12	NP_002385.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC3A2	ENST00000338663.12	TSL:1 MANE Select	c.949C>T	p.Leu317Leu	synonymous	Exon 6 of 9	ENSP00000340815.7	P08195-2
	SLC3A2	ENST00000377890.6	TSL:1	c.1252C>T	p.Leu418Leu	synonymous	Exon 9 of 12	ENSP00000367122.2	P08195-1
	SLC3A2	ENST00000377889.6	TSL:1	c.1066C>T	p.Leu356Leu	synonymous	Exon 7 of 10	ENSP00000367121.2	P08195-3

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

GnomAD2 exomes AF: 0.180 AC: 45287 AN: 251436 AF XY: 0.182

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 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

African (AFR) AF: 0.0367 AC: 1229 AN: 33480

American (AMR) AF: 0.116 AC: 5170 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 5556 AN: 26132

East Asian (EAS) AF: 0.188 AC: 7473 AN: 39700

South Asian (SAS) AF: 0.0844 AC: 7279 AN: 86258

European-Finnish (FIN) AF: 0.215 AC: 11474 AN: 53396

Middle Eastern (MID) AF: 0.195 AC: 1125 AN: 5768

European-Non Finnish (NFE) AF: 0.239 AC: 266260 AN: 1111964

Other (OTH) AF: 0.204 AC: 12345 AN: 60394

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

African (AFR) AF: 0.0463 AC: 1925 AN: 41552

American (AMR) AF: 0.151 AC: 2303 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 776 AN: 3468

East Asian (EAS) AF: 0.204 AC: 1060 AN: 5184

South Asian (SAS) AF: 0.0824 AC: 398 AN: 4828

European-Finnish (FIN) AF: 0.205 AC: 2172 AN: 10594

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15940 AN: 67992

Other (OTH) AF: 0.181 AC: 383 AN: 2114

Alfa AF: 0.213 Hom.: 7385

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.5
DANN	Benign	0.85
PhyloP100		-0.50
PromoterAI		0.051	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

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