Variant 11-62881160-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001013251.3(SLC3A2):c.137A>G(p.Lys46Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,445,650 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC3A2
NM_001013251.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.71

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC3A2	NM_001013251.3 linkuse as main transcript	c.137A>G	p.Lys46Arg	missense_variant	1/9	ENST00000338663.12
SLC3A2	NM_001012662.3 linkuse as main transcript	c.443A>G	p.Lys148Arg	missense_variant	4/12
SLC3A2	NM_002394.6 linkuse as main transcript	c.440A>G	p.Lys147Arg	missense_variant	4/12
SLC3A2	NM_001012664.3 linkuse as main transcript	c.254A>G	p.Lys85Arg	missense_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC3A2	ENST00000338663.12 linkuse as main transcript	c.137A>G	p.Lys46Arg	missense_variant	1/9	1	NM_001013251.3	P2	P08195-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1445650

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

717752

show subpopulations

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:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 02, 2023

The c.443A>G (p.K148R) alteration is located in exon 4 (coding exon 4) of the SLC3A2 gene. This alteration results from a A to G substitution at nucleotide position 443, causing the lysine (K) at amino acid position 148 to be replaced by an arginine (R). 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

0.14

BayesDel_addAF

Uncertain

0.096

BayesDel_noAF

Benign

-0.10

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.57

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

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.89

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

M_CAP

Benign

0.049

MetaRNN

Uncertain

0.43

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

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.3

M;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.6

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

REVEL

Uncertain

0.38

Sift

Uncertain

0.011

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

Sift4G

Uncertain

0.022

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

Polyphen

1.0

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

Vest4

0.34

MutPred

0.31

Loss of ubiquitination at K147 (P = 0.002);.;.;.;.;.;.;

MVP

0.78

MPC

1.3

ClinPred

0.97

GERP RS

5.0

Varity_R

0.54

gMVP

0.44

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over