Variant chrX-70928537-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032803.6(SLC7A3):c.626T>G(p.Phe209Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00012 in 1,204,397 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 42 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., 10 hem., cov: 22)

Exomes 𝑓: 0.00011 ( 0 hom. 32 hem. )

Consequence

SLC7A3
NM_032803.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11292094).

BS2

High Hemizygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A3	NM_032803.6 linkuse as main transcript	c.626T>G	p.Phe209Cys	missense_variant	4/12	ENST00000374299.8	NP_116192.4	Q8WY07
SLC7A3	NM_001048164.3 linkuse as main transcript	c.626T>G	p.Phe209Cys	missense_variant	4/12		NP_001041629.1	Q8WY07
SLC7A3	XM_047442598.1 linkuse as main transcript	c.626T>G	p.Phe209Cys	missense_variant	3/11		XP_047298554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A3	ENST00000374299.8 linkuse as main transcript	c.626T>G	p.Phe209Cys	missense_variant	4/12	1	NM_032803.6	ENSP00000363417.3		Q8WY07
SLC7A3	ENST00000298085.4 linkuse as main transcript	c.626T>G	p.Phe209Cys	missense_variant	4/12	2		ENSP00000298085.4		Q8WY07

Frequencies

GnomAD3 genomes

AF:

0.000253

AC:

AN:

110758

Hom.:

Cov.:

AF XY:

0.000303

AC XY:

AN XY:

32974

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00115

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000843

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000208

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000229

AC:

AN:

170335

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

56377

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000419

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000673

Gnomad NFE exome

AF:

0.000214

Gnomad OTH exome

AF:

0.000465

GnomAD4 exome

AF:

0.000106

AC:

116

AN:

1093639

Hom.:

Cov.:

AF XY:

0.0000890

AC XY:

AN XY:

359575

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000289

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000769

Gnomad4 NFE exome

AF:

0.0000845

Gnomad4 OTH exome

AF:

0.0000870

GnomAD4 genome

AF:

0.000253

AC:

AN:

110758

Hom.:

Cov.:

AF XY:

0.000303

AC XY:

AN XY:

32974

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00115

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000843

Gnomad4 NFE

AF:

0.000208

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000270

Hom.:

Bravo

AF:

0.000344

ExAC

AF:

0.000280

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain: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

Sep 25, 2024

The c.626T>G (p.F209C) alteration is located in exon 4 (coding exon 3) of the SLC7A3 gene. This alteration results from a T to G substitution at nucleotide position 626, causing the phenylalanine (F) at amino acid position 209 to be replaced by a cysteine (C). 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

0.28

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.74

D;D

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.92

.;D

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.11

T;T

MetaSVM

Uncertain

0.42

MutationAssessor

Pathogenic

3.1

M;M

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-5.3

D;D

REVEL

Uncertain

0.53

Sift

Benign

0.046

D;D

Sift4G

Benign

0.091

T;T

Polyphen

0.049

B;B

Vest4

0.34

MVP

0.82

MPC

1.1

ClinPred

0.28

GERP RS

3.7

Varity_R

0.71

gMVP

0.89

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