Variant X-70927999-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032803.6(SLC7A3):c.842A>G(p.Gln281Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,097,893 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 0.0 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

SLC7A3
NM_032803.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.07

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35235316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A3	NM_032803.6 linkuse as main transcript	c.842A>G	p.Gln281Arg	missense_variant	6/12	ENST00000374299.8	NP_116192.4	Q8WY07
SLC7A3	NM_001048164.3 linkuse as main transcript	c.842A>G	p.Gln281Arg	missense_variant	6/12		NP_001041629.1	Q8WY07
SLC7A3	XM_047442598.1 linkuse as main transcript	c.842A>G	p.Gln281Arg	missense_variant	5/11		XP_047298554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A3	ENST00000374299.8 linkuse as main transcript	c.842A>G	p.Gln281Arg	missense_variant	6/12	1	NM_032803.6	ENSP00000363417.3		Q8WY07
SLC7A3	ENST00000298085.4 linkuse as main transcript	c.842A>G	p.Gln281Arg	missense_variant	6/12	2		ENSP00000298085.4		Q8WY07

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

111524

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33722

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1097893

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363255

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000568

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

111524

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33722

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

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:

0.00

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

Aug 21, 2024

The c.842A>G (p.Q281R) alteration is located in exon 6 (coding exon 5) of the SLC7A3 gene. This alteration results from a A to G substitution at nucleotide position 842, causing the glutamine (Q) at amino acid position 281 to be replaced by an arginine (R). 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

0.10

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Uncertain

0.57

D;D

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.73

.;T

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.35

T;T

MetaSVM

Uncertain

0.019

MutationAssessor

Benign

1.7

L;L

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.22

Sift

Benign

0.053

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.0010

B;B

Vest4

0.24

MutPred

0.33

Gain of phosphorylation at S283 (P = 0.0709);Gain of phosphorylation at S283 (P = 0.0709);

MVP

0.59

MPC

0.48

ClinPred

0.81

GERP RS

4.1

Varity_R

0.68

gMVP

0.63

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