Genetic Variant SLC38A2:p.Asn158Asn (chr12-46367083-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_018976.5(SLC38A2):c.474C>T(p.Asn158Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00813 in 1,613,734 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0084 ( 76 hom. )

Consequence

SLC38A2
NM_018976.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.07

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 Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 12-46367083-G-A is Benign according to our data. Variant chr12-46367083-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 791632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.07 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC38A2	NM_018976.5 link	c.474C>T	p.Asn158Asn	synonymous_variant	Exon 6 of 16	ENST00000256689.10	NP_061849.2	Q96QD8-1A0A024R0W3
SLC38A2	NM_001307936.2 link	c.174C>T	p.Asn58Asn	synonymous_variant	Exon 5 of 15		NP_001294865.1	Q96QD8-2Q8NHT5
SLC38A2	XM_047429019.1 link	c.174C>T	p.Asn58Asn	synonymous_variant	Exon 3 of 13		XP_047284975.1
SLC38A2	XM_047429020.1 link	c.474C>T	p.Asn158Asn	synonymous_variant	Exon 6 of 13		XP_047284976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC38A2	ENST00000256689.10 link	c.474C>T	p.Asn158Asn	synonymous_variant	Exon 6 of 16	1	NM_018976.5	ENSP00000256689.5		Q96QD8-1

Frequencies

GnomAD3 genomes

AF:

0.00598

AC:

910

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00484

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00289

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00958

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00611

AC:

1535

AN:

251096

Hom.:

AF XY:

0.00629

AC XY:

854

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.00118

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.0163

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00232

Gnomad FIN exome

AF:

0.00394

Gnomad NFE exome

AF:

0.00907

Gnomad OTH exome

AF:

0.00768

GnomAD4 exome

AF:

0.00836

AC:

12211

AN:

1461432

Hom.:

Cov.:

AF XY:

0.00830

AC XY:

6036

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00329

Gnomad4 ASJ exome

AF:

0.0176

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00263

Gnomad4 FIN exome

AF:

0.00562

Gnomad4 NFE exome

AF:

0.00940

Gnomad4 OTH exome

AF:

0.00967

GnomAD4 genome

AF:

0.00597

AC:

910

AN:

152302

Hom.:

Cov.:

AF XY:

0.00584

AC XY:

435

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00176

Gnomad4 AMR

AF:

0.00483

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.00958

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00886

Hom.:

Bravo

AF:

0.00560

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00976

EpiControl

AF:

0.00931

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SLC38A2: BP4, BP7, BS2 -

May 03, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

9.3

DANN

Benign

0.73

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

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