Variant 8-17538911-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001164771.2(SLC7A2):c.87C>A(p.Ser29Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,612,652 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

SLC7A2
NM_001164771.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.666

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:

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=0.04476419).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A2	NM_001370338.1 linkuse as main transcript	c.-22-4407C>A		intron_variant		ENST00000494857.6	NP_001357267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A2	ENST00000494857.6 linkuse as main transcript	c.-22-4407C>A		intron_variant		5	NM_001370338.1	ENSP00000419140.2		P52569-1

Frequencies

GnomAD3 genomes

AF:

0.000803

AC:

122

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00151

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000581

AC:

145

AN:

249362

Hom.:

AF XY:

0.000621

AC XY:

AN XY:

135286

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000458

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.00140

AC:

2048

AN:

1460594

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

995

AN XY:

726664

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00174

Gnomad4 OTH exome

AF:

0.000845

GnomAD4 genome

AF:

0.000802

AC:

122

AN:

152058

Hom.:

Cov.:

AF XY:

0.000700

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000338

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00151

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000911

Hom.:

Bravo

AF:

0.000729

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00159

AC:

ExAC

AF:

0.000530

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.00160

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

Dec 02, 2024

The c.87C>A (p.S29R) alteration is located in exon 1 (coding exon 1) of the SLC7A2 gene. This alteration results from a C to A substitution at nucleotide position 87, causing the serine (S) at amino acid position 29 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

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.59

DANN

Benign

0.97

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.20

.;T;T;T

M_CAP

Pathogenic

0.29

MetaRNN

Benign

0.045

T;T;T;T

MetaSVM

Benign

-0.35

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.070

N;N;N;.

REVEL

Benign

0.20

Sift

Benign

0.075

T;T;T;.

Sift4G

Uncertain

0.034

D;D;D;.

Polyphen

0.73

P;P;P;.

Vest4

0.17

MutPred

0.32

Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);.;

MVP

0.69

MPC

0.021

ClinPred

0.030

GERP RS

1.9

gMVP

0.21

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