Variant X-102715113-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001004051.4(GPRASP2):c.244G>T(p.Gly82Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000637 in 1,098,160 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000064 ( 0 hom. 1 hem. )

Consequence

GPRASP2
NM_001004051.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.45

Variant links:

Genes affected

GPRASP2 (HGNC:25169): (G protein-coupled receptor associated sorting protein 2) The protein encoded by this gene is a member of a family that regulates the activity of G protein-coupled receptors (GPCRs). The encoded protein has been shown to be capable of interacting with several GPCRs, including the M1 muscarinic acetylcholine receptor and the calcitonin receptor. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]

GPRASP2 links:

ARMCX5-GPRASP2 (HGNC:42000): (ARMCX5-GPRASP2 readthrough) This locus represents naturally occurring readthrough transcription among the adjacent armadillo repeat containing, X-linked 5 (ARMCX5), G protein-coupled receptor associated sorting proteins 1 and 2 (GPRASP1 and GPRASP2), basic helix-loop-helix family member b9 (BHLHB9), and long intergenic non-protein coding RNA 630 (LINC00630) genes on chromosome X. Transcripts may make use of multiple alternative promoters and polyadenylation signals in this region. Readthrough transcripts may produce proteins identical to the proteins encoded by GPRASP2 or BHLHB9. [provided by RefSeq, Apr 2017]

ARMCX5-GPRASP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.053482443).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPRASP2	NM_001004051.4 linkuse as main transcript	c.244G>T	p.Gly82Cys	missense_variant	5/5	ENST00000483720.7
ARMCX5-GPRASP2	NR_146584.3 linkuse as main transcript	n.795+847G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPRASP2	ENST00000483720.7 linkuse as main transcript	c.244G>T	p.Gly82Cys	missense_variant	5/5	2	NM_001004051.4	P1
ARMCX5-GPRASP2	ENST00000652409.1 linkuse as main transcript	c.-756+847G>T		intron_variant				P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000383

AC:

AN:

182939

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67541

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000505

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000637

AC:

AN:

1098160

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363548

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000232

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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 29, 2023

The c.244G>T (p.G82C) alteration is located in exon 5 (coding exon 1) of the GPRASP2 gene. This alteration results from a G to T substitution at nucleotide position 244, causing the glycine (G) at amino acid position 82 to be replaced by a cysteine (C). 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

0.13

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.6

DANN

Benign

0.76

DEOGEN2

Benign

0.013

T;T;T

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.63

.;T;.

M_CAP

Benign

0.0080

MetaRNN

Benign

0.053

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.014

Sift

Benign

0.038

D;D;D

Sift4G

Benign

0.067

T;T;T

Polyphen

0.41

B;B;B

Vest4

0.18

MutPred

0.26

Gain of catalytic residue at G82 (P = 0.0714);Gain of catalytic residue at G82 (P = 0.0714);Gain of catalytic residue at G82 (P = 0.0714);

MVP

0.17

MPC

0.21

ClinPred

0.033

GERP RS

-0.51

Varity_R

0.20

gMVP

0.045

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