Variant X-70927535-T-C 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.1132A>G(p.Thr378Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000868 in 1,209,242 control chromosomes in the GnomAD database, including 1 homozygotes. There are 68 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.000091 ( 1 hom. 65 hem. )

Consequence

SLC7A3
NM_032803.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.419

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009606451).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC7A3	NM_032803.6 linkuse as main transcript	c.1132A>G	p.Thr378Ala	missense_variant	7/12	ENST00000374299.8
SLC7A3	NM_001048164.3 linkuse as main transcript	c.1132A>G	p.Thr378Ala	missense_variant	7/12
SLC7A3	XM_047442598.1 linkuse as main transcript	c.1132A>G	p.Thr378Ala	missense_variant	6/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A3	ENST00000374299.8 linkuse as main transcript	c.1132A>G	p.Thr378Ala	missense_variant	7/12	1	NM_032803.6	P1
SLC7A3	ENST00000298085.4 linkuse as main transcript	c.1132A>G	p.Thr378Ala	missense_variant	7/12	2		P1

Frequencies

GnomAD3 genomes

AF:

0.0000449

AC:

AN:

111428

Hom.:

Cov.:

AF XY:

0.0000892

AC XY:

AN XY:

33642

show subpopulations

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:

0.00114

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000377

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000127

AC:

AN:

181544

Hom.:

AF XY:

0.000227

AC XY:

AN XY:

66064

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000145

Gnomad SAS exome

AF:

0.00113

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000911

AC:

100

AN:

1097814

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

AN XY:

363172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00171

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.0000868

GnomAD4 genome

AF:

0.0000449

AC:

AN:

111428

Hom.:

Cov.:

AF XY:

0.0000892

AC XY:

AN XY:

33642

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00114

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000377

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.000181

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

Feb 14, 2023

The c.1132A>G (p.T378A) alteration is located in exon 7 (coding exon 6) of the SLC7A3 gene. This alteration results from a A to G substitution at nucleotide position 1132, causing the threonine (T) at amino acid position 378 to be replaced by an alanine (A). 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

0.059

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.10

DANN

Benign

0.54

DEOGEN2

Benign

0.18

T;T

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.075

.;T

M_CAP

Benign

0.043

MetaRNN

Benign

0.0096

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.54

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

0.44

N;N

REVEL

Benign

0.23

Sift

Benign

0.68

T;T

Sift4G

Benign

0.70

T;T

Polyphen

0.0

B;B

Vest4

0.066

MutPred

0.30

Loss of phosphorylation at T378 (P = 0.0373);Loss of phosphorylation at T378 (P = 0.0373);

MVP

0.34

MPC

0.32

ClinPred

0.011

GERP RS

0.95

Varity_R

0.044

gMVP

0.087

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