Variant X-70925907-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_032803.6(SLC7A3):c.1766G>C(p.Ser589Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,209,657 control chromosomes in the GnomAD database, including 7 homozygotes. There are 1,109 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., 80 hem., cov: 23)

Exomes 𝑓: 0.0028 ( 6 hom. 1029 hem. )

Consequence

SLC7A3
NM_032803.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 7.40

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021085083).

BP6

Variant X-70925907-C-G is Benign according to our data. Variant chrX-70925907-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 807745.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-70925907-C-G is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 80 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A3	NM_032803.6 linkuse as main transcript	c.1766G>C	p.Ser589Thr	missense_variant	12/12	ENST00000374299.8	NP_116192.4	Q8WY07
SLC7A3	NM_001048164.3 linkuse as main transcript	c.1766G>C	p.Ser589Thr	missense_variant	12/12		NP_001041629.1	Q8WY07
SLC7A3	XM_047442598.1 linkuse as main transcript	c.1766G>C	p.Ser589Thr	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.1766G>C	p.Ser589Thr	missense_variant	12/12	1	NM_032803.6	ENSP00000363417.3		Q8WY07
SLC7A3	ENST00000298085.4 linkuse as main transcript	c.1766G>C	p.Ser589Thr	missense_variant	12/12	2		ENSP00000298085.4		Q8WY07

Frequencies

GnomAD3 genomes

AF:

0.00238

AC:

265

AN:

111456

Hom.:

Cov.:

AF XY:

0.00241

AC XY:

AN XY:

33628

show subpopulations

Gnomad AFR

AF:

0.000882

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00374

Gnomad ASJ

AF:

0.00983

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000332

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00288

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00231

AC:

422

AN:

182326

Hom.:

AF XY:

0.00242

AC XY:

163

AN XY:

67444

show subpopulations

Gnomad AFR exome

AF:

0.000760

Gnomad AMR exome

AF:

0.00314

Gnomad ASJ exome

AF:

0.00829

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000315

Gnomad FIN exome

AF:

0.000937

Gnomad NFE exome

AF:

0.00279

Gnomad OTH exome

AF:

0.00398

GnomAD4 exome

AF:

0.00275

AC:

3025

AN:

1098150

Hom.:

Cov.:

AF XY:

0.00283

AC XY:

1029

AN XY:

363504

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.00307

Gnomad4 ASJ exome

AF:

0.0106

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.000222

Gnomad4 FIN exome

AF:

0.000691

Gnomad4 NFE exome

AF:

0.00288

Gnomad4 OTH exome

AF:

0.00349

GnomAD4 genome

AF:

0.00237

AC:

264

AN:

111507

Hom.:

Cov.:

AF XY:

0.00237

AC XY:

AN XY:

33689

show subpopulations

Gnomad4 AFR

AF:

0.000880

Gnomad4 AMR

AF:

0.00374

Gnomad4 ASJ

AF:

0.00983

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000332

Gnomad4 NFE

AF:

0.00286

Gnomad4 OTH

AF:

0.00988

Alfa

AF:

0.00368

Hom.:

Bravo

AF:

0.00290

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00346

AC:

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00342

AC:

ExAC

AF:

0.00240

AC:

291

EpiCase

AF:

0.00431

EpiControl

AF:

0.00510

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

SLC7A3: BS1 -

SLC7A3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 02, 2021

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

Uncertain

0.52

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Uncertain

0.11

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

T;T

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.79

.;T

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.021

T;T

MetaSVM

Pathogenic

0.99

MutationAssessor

Pathogenic

2.9

M;M

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-2.5

D;D

REVEL

Pathogenic

0.78

Sift

Uncertain

0.020

D;D

Sift4G

Uncertain

0.018

D;D

Polyphen

0.94

P;P

Vest4

0.71

MVP

0.94

MPC

0.81

ClinPred

0.027

GERP RS

4.8

Varity_R

0.68

gMVP

0.86

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