Variant 11-62881177-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001013251.3(SLC3A2):c.154G>A(p.Ala52Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000663 in 150,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC3A2
NM_001013251.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.096585184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC3A2	NM_001013251.3 linkuse as main transcript	c.154G>A	p.Ala52Thr	missense_variant	1/9	ENST00000338663.12	NP_001013269.1	P08195-2
SLC3A2	NM_001012662.3 linkuse as main transcript	c.460G>A	p.Ala154Thr	missense_variant	4/12		NP_001012680.1	P08195-5
SLC3A2	NM_002394.6 linkuse as main transcript	c.457G>A	p.Ala153Thr	missense_variant	4/12		NP_002385.3	P08195-1
SLC3A2	NM_001012664.3 linkuse as main transcript	c.271G>A	p.Ala91Thr	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.154G>A	p.Ala52Thr	missense_variant	1/9	1	NM_001013251.3	ENSP00000340815.7		P08195-2

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1442966

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716022

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150900

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73744

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

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

Oct 12, 2024

The c.460G>A (p.A154T) alteration is located in exon 4 (coding exon 4) of the SLC3A2 gene. This alteration results from a G to A substitution at nucleotide position 460, causing the alanine (A) at amino acid position 154 to be replaced by a threonine (T). 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

0.077

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

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

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.75

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

M_CAP

Benign

0.078

MetaRNN

Benign

0.097

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

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.81

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

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.39

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

REVEL

Benign

0.095

Sift

Benign

0.54

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

Sift4G

Benign

0.48

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

Polyphen

0.16

B;.;B;B;.;B;.

Vest4

0.17

MutPred

0.30

Gain of phosphorylation at A153 (P = 0.0262);.;.;.;.;.;.;

MVP

0.48

MPC

0.57

ClinPred

0.078

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.036

gMVP

0.14

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