Genetic Variant NM_001013251.3:c.112G>A (chr11-62881135-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001013251.3(SLC3A2):c.112G>A(p.Glu38Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,004 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E38Q) has been classified 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

Not reported in ClinVar

Conservation

PhyloP100: 8.31

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 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.112G>A	p.Glu38Lys	missense_variant	Exon 1 of 9	ENST00000338663.12	NP_001013269.1	P08195-2
SLC3A2	NM_001012662.3 link	c.418G>A	p.Glu140Lys	missense_variant	Exon 4 of 12		NP_001012680.1	P08195-5
SLC3A2	NM_002394.6 link	c.415G>A	p.Glu139Lys	missense_variant	Exon 4 of 12		NP_002385.3	P08195-1
SLC3A2	NM_001012664.3 link	c.229G>A	p.Glu77Lys	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.112G>A	p.Glu38Lys	missense_variant	Exon 1 of 9	1	NM_001013251.3	ENSP00000340815.7		P08195-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1452004

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721382

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33450

American (AMR)

AF:

0.00

AC:

AN:

41780

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25752

East Asian (EAS)

AF:

0.00

AC:

AN:

39328

South Asian (SAS)

AF:

0.00

AC:

AN:

84446

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52706

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108690

Other (OTH)

AF:

0.00

AC:

AN:

60102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.61

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

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.91

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

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.67

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

MetaSVM

Uncertain

0.085

MutationAssessor

Benign

1.8

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

PhyloP100

8.3

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-2.0

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

REVEL

Uncertain

0.55

Sift

Benign

0.042

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

Sift4G

Uncertain

0.013

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

Polyphen

0.99

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

Vest4

0.67

MutPred

0.34

Gain of MoRF binding (P = 0.0045);.;.;.;.;.;.;

MVP

0.90

MPC

1.5

ClinPred

0.98

GERP RS

5.0

PromoterAI

-0.031

Neutral

(source)

Varity_R

0.41

gMVP

0.65

Mutation Taster

=59/41

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over