11-62881276-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001013251.3(SLC3A2):c.253C>T(p.Leu85=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00384 in 1,589,912 control chromosomes in the GnomAD database, including 188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (93 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (95 hom.)
• Consequence: SLC3A2 NM_001013251.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.86

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 11-62881276-C-T is Benign according to our data. Variant chr11-62881276-C-T is described in ClinVar as [Benign]. Clinvar id is 789624.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC3A2	NM_001013251.3	c.253C>T	p.Leu85=	synonymous_variant	1/9	ENST00000338663.12
SLC3A2	NM_001012662.3	c.559C>T	p.Leu187=	synonymous_variant	4/12
SLC3A2	NM_002394.6	c.556C>T	p.Leu186=	synonymous_variant	4/12
SLC3A2	NM_001012664.3	c.370C>T	p.Leu124=	synonymous_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC3A2	ENST00000338663.12	c.253C>T	p.Leu85=	synonymous_variant	1/9	1	NM_001013251.3	P2

Frequencies

GnomAD3 genomes AF: 0.0195 AC: 2976 AN: 152254 Hom.: 93 Cov.: 32

Gnomad AFR AF: 0.0672

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.00476 AC: 985 AN: 206764 Hom.: 27 AF XY: 0.00353 AC XY: 394 AN XY: 111552

Gnomad AFR exome AF: 0.0685

Gnomad AMR exome AF: 0.00333

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000749

Gnomad FIN exome AF: 0.0000583

Gnomad NFE exome AF: 0.000219

Gnomad OTH exome AF: 0.00325

GnomAD4 exome AF: 0.00217 AC: 3125 AN: 1437540 Hom.: 95 Cov.: 31 AF XY: 0.00185 AC XY: 1320 AN XY: 712894

Gnomad4 AFR exome AF: 0.0765

Gnomad4 AMR exome AF: 0.00407

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000843

Gnomad4 FIN exome AF: 0.0000196

Gnomad4 NFE exome AF: 0.000148

Gnomad4 OTH exome AF: 0.00414

GnomAD4 genome AF: 0.0195 AC: 2978 AN: 152372 Hom.: 93 Cov.: 32 AF XY: 0.0190 AC XY: 1413 AN XY: 74510

Gnomad4 AFR AF: 0.0671

Gnomad4 AMR AF: 0.00777

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.0165

Alfa AF: 0.00540 Hom.: 9

Bravo AF: 0.0229

Asia WGS AF: 0.00433 AC: 16 AN: 3478

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

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
Cadd	Benign	15
Dann	Benign	0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs73487878; hg19: chr11-62648748;