Variant X-70928912-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_032803.6(SLC7A3):c.461T>C(p.Leu154Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000048 in 1,209,179 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000047 ( 0 hom. 19 hem. )

Consequence

SLC7A3
NM_032803.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.92

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.32329875).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC7A3	NM_032803.6 linkuse as main transcript	c.461T>C	p.Leu154Pro	missense_variant	3/12	ENST00000374299.8
SLC7A3	NM_001048164.3 linkuse as main transcript	c.461T>C	p.Leu154Pro	missense_variant	3/12
SLC7A3	XM_047442598.1 linkuse as main transcript	c.461T>C	p.Leu154Pro	missense_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A3	ENST00000374299.8 linkuse as main transcript	c.461T>C	p.Leu154Pro	missense_variant	3/12	1	NM_032803.6	P1
SLC7A3	ENST00000298085.4 linkuse as main transcript	c.461T>C	p.Leu154Pro	missense_variant	3/12	2		P1

Frequencies

GnomAD3 genomes

AF:

0.0000539

AC:

AN:

111394

Hom.:

Cov.:

AF XY:

0.0000596

AC XY:

AN XY:

33570

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00151

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000377

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000872

AC:

AN:

183424

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

67858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00174

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.000442

GnomAD4 exome

AF:

0.0000474

AC:

AN:

1097785

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

363143

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00160

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000178

Gnomad4 OTH exome

AF:

0.000130

GnomAD4 genome

AF:

0.0000539

AC:

AN:

111394

Hom.:

Cov.:

AF XY:

0.0000596

AC XY:

AN XY:

33570

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00151

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000377

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000304

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.0000824

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

Oct 25, 2022

The c.461T>C (p.L154P) alteration is located in exon 3 (coding exon 2) of the SLC7A3 gene. This alteration results from a T to C substitution at nucleotide position 461, causing the leucine (L) at amino acid position 154 to be replaced by a proline (P). 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

0.12

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Uncertain

0.58

D;D

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.51

.;T

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-0.40

MutationAssessor

Benign

0.075

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.2

D;D

REVEL

Uncertain

0.33

Sift

Benign

0.22

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.0040

B;B

Vest4

0.63

MVP

0.73

MPC

0.55

ClinPred

0.11

GERP RS

4.0

Varity_R

0.58

gMVP

0.87

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