Variant 11-62881135-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001013251.3(SLC3A2):c.112G>C(p.Glu38Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000368 in 1,604,238 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

SLC3A2
NM_001013251.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.31

Variant links:

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]

SLC3A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC3A2	NM_001013251.3 linkuse as main transcript	c.112G>C	p.Glu38Gln	missense_variant	1/9	ENST00000338663.12
SLC3A2	NM_001012662.3 linkuse as main transcript	c.418G>C	p.Glu140Gln	missense_variant	4/12
SLC3A2	NM_002394.6 linkuse as main transcript	c.415G>C	p.Glu139Gln	missense_variant	4/12
SLC3A2	NM_001012664.3 linkuse as main transcript	c.229G>C	p.Glu77Gln	missense_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC3A2	ENST00000338663.12 linkuse as main transcript	c.112G>C	p.Glu38Gln	missense_variant	1/9	1	NM_001013251.3	P2	P08195-2

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

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:

0.00143

GnomAD3 exomes

AF:

0.0000305

AC:

AN:

229716

Hom.:

AF XY:

0.0000242

AC XY:

AN XY:

123906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000973

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000192

Gnomad OTH exome

AF:

0.000356

GnomAD4 exome

AF:

0.0000262

AC:

AN:

1452004

Hom.:

Cov.:

AF XY:

0.0000222

AC XY:

AN XY:

721382

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000455

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000138

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00111

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:

0.00143

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.000272

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 17, 2023

The c.418G>C (p.E140Q) alteration is located in exon 4 (coding exon 4) of the SLC3A2 gene. This alteration results from a G to C substitution at nucleotide position 418, causing the glutamic acid (E) at amino acid position 140 to be replaced by a glutamine (Q). 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

Uncertain

0.35

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Uncertain

0.030

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;.;.;.;.;.;T

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.87

D;D;D;D;D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.54

D;D;D;D;D;D;D

MetaSVM

Uncertain

0.15

MutationAssessor

Benign

1.8

L;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.6

N;N;N;N;N;N;N

REVEL

Uncertain

0.47

Sift

Uncertain

0.0050

D;D;D;D;T;D;D

Sift4G

Uncertain

0.0090

D;D;D;D;D;D;D

Polyphen

1.0

D;.;D;D;.;D;.

Vest4

0.51

MutPred

0.30

Gain of MoRF binding (P = 0.0222);.;.;.;.;.;.;

MVP

0.87

MPC

1.4

ClinPred

0.79

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.49

gMVP

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over