Genetic Variant SLC38A2:p.Thr262Ser (chr12-46364478-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018976.5(SLC38A2):c.784A>T(p.Thr262Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC38A2
NM_018976.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.347

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06415039).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC38A2	NM_018976.5 link	c.784A>T	p.Thr262Ser	missense_variant	Exon 10 of 16	ENST00000256689.10	NP_061849.2	Q96QD8-1A0A024R0W3
SLC38A2	NM_001307936.2 link	c.484A>T	p.Thr162Ser	missense_variant	Exon 9 of 15		NP_001294865.1	Q96QD8-2Q8NHT5
SLC38A2	XM_047429019.1 link	c.484A>T	p.Thr162Ser	missense_variant	Exon 7 of 13		XP_047284975.1
SLC38A2	XM_047429020.1 link	c.784A>T	p.Thr262Ser	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.784A>T	p.Thr262Ser	missense_variant	Exon 10 of 16	1	NM_018976.5	ENSP00000256689.5		Q96QD8-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460906

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726736

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000132

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.784A>T (p.T262S) alteration is located in exon 10 (coding exon 9) of the SLC38A2 gene. This alteration results from a A to T substitution at nucleotide position 784, causing the threonine (T) at amino acid position 262 to be replaced by a serine (S). 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

0.066

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.31

DANN

Benign

0.87

DEOGEN2

Benign

0.011

T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.41

T;T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.064

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.26

N;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.11

N;N;.

REVEL

Benign

0.013

Sift

Benign

0.87

T;T;.

Sift4G

Benign

0.84

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.22

MutPred

0.45

Loss of glycosylation at T262 (P = 0.093);.;.;

MVP

0.27

MPC

0.17

ClinPred

0.097

GERP RS

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.070

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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