Genetic Variant SLC3A2:p.Gly76Val (chr11-62881250-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001013251.3(SLC3A2):c.227G>T(p.Gly76Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,432,002 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: 0.0000021 ( 0 hom. )

Consequence

SLC3A2
NM_001013251.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.588

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 rank	MANE	Protein	UniProt
SLC3A2	NM_001013251.3 link	c.227G>T	p.Gly76Val	missense_variant	Exon 1 of 9	ENST00000338663.12	NP_001013269.1	P08195-2
SLC3A2	NM_001012662.3 link	c.533G>T	p.Gly178Val	missense_variant	Exon 4 of 12		NP_001012680.1	P08195-5
SLC3A2	NM_002394.6 link	c.530G>T	p.Gly177Val	missense_variant	Exon 4 of 12		NP_002385.3	P08195-1
SLC3A2	NM_001012664.3 link	c.344G>T	p.Gly115Val	missense_variant	Exon 2 of 10		NP_001012682.1	P08195-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC3A2	ENST00000338663.12 link	c.227G>T	p.Gly76Val	missense_variant	Exon 1 of 9	1	NM_001013251.3	ENSP00000340815.7		P08195-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000507

AC:

AN:

197370

Hom.:

AF XY:

0.00000946

AC XY:

AN XY:

105750

show subpopulations

Gnomad AFR exome

AF:

0.0000840

Gnomad AMR exome

AF:

0.00

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:

0.00000209

AC:

AN:

1432002

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

709330

show subpopulations

Gnomad4 AFR exome

AF:

0.0000604

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:

9.10e-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

Aug 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.533G>T (p.G178V) 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 533, causing the glycine (G) at amino acid position 178 to be replaced by a valine (V). 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

0.19

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.59

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

Eigen

Benign

0.10

Eigen_PC

Benign

0.033

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.78

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

M_CAP

Pathogenic

0.51

MetaRNN

Uncertain

0.44

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

MetaSVM

Uncertain

-0.16

MutationAssessor

Benign

2.0

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

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.6

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

REVEL

Uncertain

0.41

Sift

Uncertain

0.023

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

Sift4G

Uncertain

0.010

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

Polyphen

1.0

D;.;P;P;.;D;.;.

Vest4

0.37

MutPred

0.28

Loss of helix (P = 0.0093);.;.;.;.;.;.;.;

MVP

0.61

MPC

1.5

ClinPred

0.98

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.47

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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