Variant 8-17543652-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3BP4_StrongBP6_ModerateBS2

The NM_001370338.1(SLC7A2):c.313G>C(p.Val105Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,551,144 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 28 hom. )

Consequence

SLC7A2
NM_001370338.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.96

Variant links:

Genes affected

SLC7A2 (HGNC:11060): (solute carrier family 7 member 2) The protein encoded by this gene is a cationic amino acid transporter and a member of the APC (amino acid-polyamine-organocation) family of transporters. The encoded membrane protein is responsible for the cellular uptake of arginine, lysine and ornithine. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

SLC7A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 6: AlphaMissense, BayesDel_noAF, Eigen, MutationAssessor, phyloP100way_vertebrate, PrimateAI [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.010587305).

BP6

Variant 8-17543652-G-C is Benign according to our data. Variant chr8-17543652-G-C is described in ClinVar as [Benign]. Clinvar id is 3042141.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A2	NM_001370338.1 linkuse as main transcript	c.313G>C	p.Val105Leu	missense_variant	3/13	ENST00000494857.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A2	ENST00000494857.6 linkuse as main transcript	c.313G>C	p.Val105Leu	missense_variant	3/13	5	NM_001370338.1	P4	P52569-1

Frequencies

GnomAD3 genomes

AF:

0.00196

AC:

298

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00750

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0166

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00218

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00375

AC:

735

AN:

196144

Hom.:

AF XY:

0.00442

AC XY:

458

AN XY:

103734

show subpopulations

Gnomad AFR exome

AF:

0.000320

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.0101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0158

Gnomad FIN exome

AF:

0.00104

Gnomad NFE exome

AF:

0.00351

Gnomad OTH exome

AF:

0.00477

GnomAD4 exome

AF:

0.00289

AC:

4040

AN:

1398900

Hom.:

Cov.:

AF XY:

0.00330

AC XY:

2276

AN XY:

689128

show subpopulations

Gnomad4 AFR exome

AF:

0.000349

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.00857

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0152

Gnomad4 FIN exome

AF:

0.00109

Gnomad4 NFE exome

AF:

0.00221

Gnomad4 OTH exome

AF:

0.00319

GnomAD4 genome

AF:

0.00196

AC:

298

AN:

152244

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

170

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00750

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0166

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.00218

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00219

Hom.:

Bravo

AF:

0.00169

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.00414

AC:

501

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SLC7A2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 11, 2019

This variant is classified as 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

Pathogenic

0.92

BayesDel_addAF

Uncertain

0.048

BayesDel_noAF

Pathogenic

0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.70

D;D;.;.;.;.

Eigen

Pathogenic

0.75

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.99

MetaRNN

Benign

0.011

T;T;T;T;T;T

MetaSVM

Pathogenic

0.91

MutationAssessor

Pathogenic

3.0

M;M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-2.6

D;D;D;D;D;.

REVEL

Uncertain

0.62

Sift

Uncertain

0.027

D;D;D;D;D;.

Sift4G

Uncertain

0.0030

D;D;D;D;D;.

Polyphen

1.0

D;D;D;D;D;.

Vest4

0.85

MutPred

0.63

Loss of catalytic residue at V105 (P = 0.0784);Loss of catalytic residue at V105 (P = 0.0784);.;.;.;.;

MVP

0.89

MPC

0.17

ClinPred

0.064

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.41

gMVP

0.83

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