Genetic Variant SLC38A2:p.Asp279Tyr (chr12-46364427-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_018976.5(SLC38A2):c.835G>T(p.Asp279Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,449,572 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: 0.000019 ( 0 hom. )

Consequence

SLC38A2
NM_018976.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66

Variant links:

Genes affected

SLC38A2 (HGNC:13448): (solute carrier family 38 member 2) Enables neutral amino acid:sodium symporter activity. Involved in several processes, including amino acid transport; cellular response to arsenite(3-); and positive regulation of RNA splicing. Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC38A2 links:

Genome browser will be placed here

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
SLC38A2	NM_018976.5 link	c.835G>T	p.Asp279Tyr	missense_variant	Exon 10 of 16	ENST00000256689.10	NP_061849.2	Q96QD8-1A0A024R0W3
SLC38A2	NM_001307936.2 link	c.535G>T	p.Asp179Tyr	missense_variant	Exon 9 of 15		NP_001294865.1	Q96QD8-2Q8NHT5
SLC38A2	XM_047429019.1 link	c.535G>T	p.Asp179Tyr	missense_variant	Exon 7 of 13		XP_047284975.1
SLC38A2	XM_047429020.1 link	c.835G>T	p.Asp279Tyr	missense_variant	Exon 10 of 13		XP_047284976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC38A2	ENST00000256689.10 link	c.835G>T	p.Asp279Tyr	missense_variant	Exon 10 of 16	1	NM_018976.5	ENSP00000256689.5		Q96QD8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000377

AC:

AN:

238724

Hom.:

AF XY:

0.0000542

AC XY:

AN XY:

129058

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000186

AC:

AN:

1449572

Hom.:

Cov.:

AF XY:

0.0000222

AC XY:

AN XY:

720936

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:

0.000312

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.835G>T (p.D279Y) alteration is located in exon 10 (coding exon 9) of the SLC38A2 gene. This alteration results from a G to T substitution at nucleotide position 835, causing the aspartic acid (D) at amino acid position 279 to be replaced by a tyrosine (Y). 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

0.11

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;.;.

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.062

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.055

MetaRNN

Uncertain

0.67

D;D;D

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.7

M;.;.

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.5

D;D;.

REVEL

Benign

0.26

Sift

Uncertain

0.0010

D;D;.

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

0.99

D;P;D

Vest4

0.73

MutPred

0.52

Loss of disorder (P = 0.0283);.;.;

MVP

0.043

MPC

0.73

ClinPred

0.57

GERP RS

5.7

Varity_R

0.49

gMVP

0.87

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