8-86217503-T-G

Position:

chr8-86217503-T-G

Variant summary

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

The NM_138817.3(SLC7A13):c.1146A>C(p.Arg382Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,594,162 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

SLC7A13
NM_138817.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.0240

Variant links:

Genes affected

SLC7A13 (HGNC:23092): (solute carrier family 7 member 13) Predicted to enable L-amino acid transmembrane transporter activity. Predicted to be involved in L-cystine transport; L-glutamate transmembrane transport; and aspartate transmembrane transport. Predicted to be integral component of membrane. Predicted to be active in apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC7A13 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/exons	MANE	Protein	UniProt
SLC7A13	NM_138817.3 linkuse as main transcript	c.1146A>C	p.Arg382Ser	missense_variant	3/4	ENST00000297524.8	NP_620172.2	Q8TCU3-1
SLC7A13	XM_011516867.3 linkuse as main transcript	c.1119A>C	p.Arg373Ser	missense_variant	3/4		XP_011515169.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A13	ENST00000297524.8 linkuse as main transcript	c.1146A>C	p.Arg382Ser	missense_variant	3/4	1	NM_138817.3	ENSP00000297524.3		Q8TCU3-1
SLC7A13	ENST00000419776.2 linkuse as main transcript	c.1119A>C	p.Arg373Ser	missense_variant	3/5	1		ENSP00000410982.2		Q8TCU3-2

Frequencies

GnomAD3 genomes

AF:

0.000486

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.000958

GnomAD3 exomes

AF:

0.0000949

AC:

AN:

231846

Hom.:

AF XY:

0.0000478

AC XY:

AN XY:

125492

show subpopulations

Gnomad AFR exome

AF:

0.00137

Gnomad AMR exome

AF:

0.0000328

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000694

AC:

100

AN:

1441908

Hom.:

Cov.:

AF XY:

0.0000614

AC XY:

AN XY:

716788

show subpopulations

Gnomad4 AFR exome

AF:

0.00232

Gnomad4 AMR exome

AF:

0.0000498

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000243

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.05e-7

Gnomad4 OTH exome

AF:

0.000336

GnomAD4 genome

AF:

0.000493

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.0000655

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:

0.000948

Alfa

AF:

0.000105

Hom.:

Bravo

AF:

0.000555

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2021

The c.1146A>C (p.R382S) alteration is located in exon 3 (coding exon 3) of the SLC7A13 gene. This alteration results from a A to C substitution at nucleotide position 1146, causing the arginine (R) at amino acid position 382 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 16, 2024

This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 382 of the SLC7A13 protein (p.Arg382Ser). This variant is present in population databases (rs140915018, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SLC7A13-related conditions. ClinVar contains an entry for this variant (Variation ID: 2163371). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Uncertain

0.079

BayesDel_noAF

Pathogenic

0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.56

D;.

Eigen

Benign

0.030

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.77

T;T

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.71

D;D

MetaSVM

Uncertain

0.78

MutationAssessor

Pathogenic

3.5

M;.

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-5.0

D;D

REVEL

Pathogenic

0.66

Sift

Uncertain

0.0020

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.63

MutPred

0.77

Loss of stability (P = 0.0699);.;

MVP

0.39

MPC

0.050

ClinPred

0.48

GERP RS

-1.4

Varity_R

0.87

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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