Variant 8-17543614-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001370338.1(SLC7A2):c.275G>A(p.Arg92His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000152 in 1,448,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

SLC7A2
NM_001370338.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U: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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.9

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A2	NM_001370338.1 linkuse as main transcript	c.275G>A	p.Arg92His	missense_variant	3/13	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.275G>A	p.Arg92His	missense_variant	3/13	5	NM_001370338.1	ENSP00000419140.2		P52569-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000168

AC:

AN:

237474

Hom.:

AF XY:

0.0000235

AC XY:

AN XY:

127730

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000305

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000551

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000152

AC:

AN:

1448086

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

719196

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000232

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000118

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

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

Jun 02, 2023

The c.395G>A (p.R132H) alteration is located in exon 2 (coding exon 2) of the SLC7A2 gene. This alteration results from a G to A substitution at nucleotide position 395, causing the arginine (R) at amino acid position 132 to be replaced by a histidine (H). 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

Pathogenic

0.86

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.40

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.77

D;D;.;.;.;.

Eigen

Pathogenic

0.97

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

.;D;.;D;D;D

M_CAP

Uncertain

0.21

MetaRNN

Pathogenic

0.90

D;D;D;D;D;D

MetaSVM

Pathogenic

0.96

MutationAssessor

Pathogenic

3.5

M;M;.;.;.;.

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-4.6

D;D;D;D;D;.

REVEL

Pathogenic

0.84

Sift

Uncertain

0.0020

D;D;D;D;D;.

Sift4G

Pathogenic

0.0010

D;D;D;D;D;.

Polyphen

1.0

D;D;D;D;D;.

Vest4

0.77

MutPred

0.62

Loss of methylation at R92 (P = 0.0477);Loss of methylation at R92 (P = 0.0477);.;.;.;.;

MVP

0.99

MPC

0.18

ClinPred

0.98

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.48

gMVP

0.86

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