11-62881102-G-T

Variant names:

• chr11-62881102-G-T
• rs757945289
• NM_001013251.3:c.79G>T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001013251.3(SLC3A2):​c.79G>T​(p.Ala27Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000267 in 1,608,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: SLC3A2 NM_001013251.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.90

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.029641569).
• BS2: High AC in GnomAd4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC3A2	NM_001013251.3	c.79G>T	p.Ala27Ser	missense_variant	Exon 1 of 9	ENST00000338663.12	NP_001013269.1
SLC3A2	NM_001012662.3	c.385G>T	p.Ala129Ser	missense_variant	Exon 4 of 12		NP_001012680.1
SLC3A2	NM_002394.6	c.382G>T	p.Ala128Ser	missense_variant	Exon 4 of 12		NP_002385.3
SLC3A2	NM_001012664.3	c.196G>T	p.Ala66Ser	missense_variant	Exon 2 of 10		NP_001012682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC3A2	ENST00000338663.12	c.79G>T	p.Ala27Ser	missense_variant	Exon 1 of 9	1	NM_001013251.3	ENSP00000340815.7

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152268 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000225 AC: 54 AN: 239612 Hom.: 0 AF XY: 0.000255 AC XY: 33 AN XY: 129336

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.0000302

Gnomad ASJ exome AF: 0.00323

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000281 AC: 409 AN: 1456328 Hom.: 0 Cov.: 31 AF XY: 0.000311 AC XY: 225 AN XY: 723650

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000686

Gnomad4 ASJ exome AF: 0.00283

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000282

Gnomad4 OTH exome AF: 0.000299

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152268 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74388

Gnomad4 AFR AF: 0.0000965

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000393 Hom.: 0

Bravo AF: 0.000162

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ExAC AF: 0.000140 AC: 17

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.385G>T (p.A129S) alteration is located in exon 4 (coding exon 4) of the SLC3A2 gene. This alteration results from a G to T substitution at nucleotide position 385, causing the alanine (A) at amino acid position 129 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;.;.;.;.;.;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.76	T;T;T;T;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.030	T;T;T;T;T;T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.5	L;.;.;.;.;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.37	N;N;N;N;N;N;N
REVEL	Benign	0.26
Sift	Benign	0.14	T;T;T;T;T;T;T
Sift4G	Benign	0.22	T;T;T;T;T;T;T
Polyphen		0.49	P;.;D;P;.;P;.
Vest4		0.22
MVP		0.76
MPC		0.95
ClinPred		0.14	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.13

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: rs757945289; hg19: chr11-62648574;