Variant 11-62881108-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001013251.3(SLC3A2):c.85G>T(p.Gly29Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,608,696 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SLC3A2
NM_001013251.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.79

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:

SLC3A2 (HGNC:):

SLC3A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26536208).

BS2

High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC3A2	NM_001013251.3 linkuse as main transcript	c.85G>T	p.Gly29Trp	missense_variant	1/9	ENST00000338663.12	NP_001013269.1	P08195-2
SLC3A2	NM_001012662.3 linkuse as main transcript	c.391G>T	p.Gly131Trp	missense_variant	4/12		NP_001012680.1	P08195-5
SLC3A2	NM_002394.6 linkuse as main transcript	c.388G>T	p.Gly130Trp	missense_variant	4/12		NP_002385.3	P08195-1
SLC3A2	NM_001012664.3 linkuse as main transcript	c.202G>T	p.Gly68Trp	missense_variant	2/10		NP_001012682.1	P08195-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC3A2	ENST00000338663.12 linkuse as main transcript	c.85G>T	p.Gly29Trp	missense_variant	1/9	1	NM_001013251.3	ENSP00000340815.7		P08195-2

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000956

GnomAD3 exomes

AF:

0.0000418

AC:

AN:

238960

Hom.:

AF XY:

0.0000388

AC XY:

AN XY:

128988

show subpopulations

Gnomad AFR exome

AF:

0.000521

Gnomad AMR exome

AF:

0.0000606

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1456446

Hom.:

Cov.:

AF XY:

0.00000967

AC XY:

AN XY:

723808

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.0000915

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000171

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.000555

Gnomad4 AMR

AF:

0.0000654

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:

0.000956

Alfa

AF:

0.000197

Hom.:

Bravo

AF:

0.000230

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000413

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

Jul 10, 2024

The c.391G>T (p.G131W) 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 391, causing the glycine (G) at amino acid position 131 to be replaced by a tryptophan (W). 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

0.39

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.73

D;.;.;.;.;.;T

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.87

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

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.27

T;T;T;T;T;T;T

MetaSVM

Benign

-0.37

MutationAssessor

Benign

1.1

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

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.8

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

REVEL

Uncertain

0.32

Sift

Uncertain

0.014

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

Sift4G

Uncertain

0.0040

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

Polyphen

0.99

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

Vest4

0.39

MVP

0.82

MPC

1.5

ClinPred

0.30

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.28

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