Genetic Variant SLC38A2:p.Ile374Val (chr12-46363080-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018976.5(SLC38A2):c.1120A>G(p.Ile374Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,460,960 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: not found (cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

SLC38A2
NM_018976.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.576

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0712364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC38A2	NM_018976.5 link	c.1120A>G	p.Ile374Val	missense_variant	Exon 13 of 16	ENST00000256689.10	NP_061849.2	Q96QD8-1A0A024R0W3
SLC38A2	NM_001307936.2 link	c.820A>G	p.Ile274Val	missense_variant	Exon 12 of 15		NP_001294865.1	Q96QD8-2Q8NHT5
SLC38A2	XM_047429019.1 link	c.820A>G	p.Ile274Val	missense_variant	Exon 10 of 13		XP_047284975.1
SLC38A2	XM_047429020.1 link	c.1055-442A>G		intron_variant	Intron 12 of 12		XP_047284976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC38A2	ENST00000256689.10 link	c.1120A>G	p.Ile374Val	missense_variant	Exon 13 of 16	1	NM_018976.5	ENSP00000256689.5		Q96QD8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

251006

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135670

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1460960

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726786

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:

0.0000225

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000625

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000546

EpiControl

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

May 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1120A>G (p.I374V) alteration is located in exon 13 (coding exon 12) of the SLC38A2 gene. This alteration results from a A to G substitution at nucleotide position 1120, causing the isoleucine (I) at amino acid position 374 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

0.062

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.016

T;.;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.071

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.55

N;.;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.010

N;N;.

REVEL

Benign

0.091

Sift

Benign

0.38

T;T;.

Sift4G

Benign

0.93

T;T;T

Polyphen

0.0020

B;B;B

Vest4

0.093

MutPred

0.70

Gain of helix (P = 0.0425);.;.;

MVP

0.043

MPC

0.16

ClinPred

0.090

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.076

gMVP

0.16

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

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