Variant X-70925875-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_032803.6(SLC7A3):c.1798C>T(p.Arg600Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000576 in 1,209,290 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 212 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., 6 hem., cov: 22)

Exomes 𝑓: 0.00061 ( 0 hom. 206 hem. )

Consequence

SLC7A3
NM_032803.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 0.749

Variant links:

Genes affected

SLC7A3 (HGNC:11061): (solute carrier family 7 member 3) This gene encodes a member of the solute carrier family 7. The encoded protein is a sodium-independent cationic amino acid transporter. Alternate splicing results in multiple transcripts that encoded the same protein.[provided by RefSeq, May 2010]

SLC7A3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.045600623).

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A3	NM_032803.6 linkuse as main transcript	c.1798C>T	p.Arg600Cys	missense_variant	12/12	ENST00000374299.8	NP_116192.4	Q8WY07
SLC7A3	NM_001048164.3 linkuse as main transcript	c.1798C>T	p.Arg600Cys	missense_variant	12/12		NP_001041629.1	Q8WY07
SLC7A3	XM_047442598.1 linkuse as main transcript	c.1798C>T	p.Arg600Cys	missense_variant	11/11		XP_047298554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A3	ENST00000374299.8 linkuse as main transcript	c.1798C>T	p.Arg600Cys	missense_variant	12/12	1	NM_032803.6	ENSP00000363417.3		Q8WY07
SLC7A3	ENST00000298085.4 linkuse as main transcript	c.1798C>T	p.Arg600Cys	missense_variant	12/12	2		ENSP00000298085.4		Q8WY07

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

111375

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

AN XY:

33559

show subpopulations

Gnomad AFR

AF:

0.0000654

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000962

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000564

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000452

Gnomad OTH

AF:

0.000666

GnomAD3 exomes

AF:

0.000301

AC:

AN:

182447

Hom.:

AF XY:

0.000341

AC XY:

AN XY:

67469

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000505

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000531

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000608

AC:

667

AN:

1097915

Hom.:

Cov.:

AF XY:

0.000567

AC XY:

206

AN XY:

363271

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000331

Gnomad4 SAS exome

AF:

0.0000739

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000744

Gnomad4 OTH exome

AF:

0.000499

GnomAD4 genome

AF:

0.000269

AC:

AN:

111375

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

AN XY:

33559

show subpopulations

Gnomad4 AFR

AF:

0.0000654

Gnomad4 AMR

AF:

0.0000962

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000564

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000452

Gnomad4 OTH

AF:

0.000666

Alfa

AF:

0.000400

Hom.:

Bravo

AF:

0.000351

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000313

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000533

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 08, 2022

The c.1798C>T (p.R600C) alteration is located in exon 12 (coding exon 11) of the SLC7A3 gene. This alteration results from a C to T substitution at nucleotide position 1798, causing the arginine (R) at amino acid position 600 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

SLC7A3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 07, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.59

CADD

Benign

6.0

DANN

Benign

0.97

DEOGEN2

Benign

0.046

T;T

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.59

.;T

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.046

T;T

MetaSVM

Benign

-0.55

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

0.82

N;N

REVEL

Benign

0.22

Sift

Benign

0.053

T;T

Sift4G

Benign

0.063

T;T

Polyphen

0.74

P;P

Vest4

0.062

MVP

0.26

MPC

0.45

ClinPred

0.039

GERP RS

-0.28

Varity_R

0.064

gMVP

0.21

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