X-102715195-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001004051.4(GPRASP2):c.326G>A(p.Arg109His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,211,722 control chromosomes in the GnomAD database, including 3 homozygotes. There are 806 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00093 ( 0 hom., 26 hem., cov: 24)

Exomes 𝑓: 0.0023 ( 3 hom. 780 hem. )

Consequence

GPRASP2
NM_001004051.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.60

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 Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012194544).

BP6

Variant X-102715195-G-A is Benign according to our data. Variant chrX-102715195-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3053315.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-102715195-G-A is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 26 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRASP2	NM_001004051.4 link	c.326G>A	p.Arg109His	missense_variant	Exon 5 of 5	ENST00000483720.7	NP_001004051.1	Q96D09B3KW05

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPRASP2	ENST00000483720.7 link	c.326G>A	p.Arg109His	missense_variant	Exon 5 of 5	2	NM_001004051.4	ENSP00000507692.1		Q96D09
ARMCX5-GPRASP2	ENST00000652409.1 link	c.-756+929G>A		intron_variant	Intron 4 of 7			ENSP00000498643.1

Frequencies

GnomAD3 genomes

AF:

0.000934

AC:

106

AN:

113465

Hom.:

Cov.:

AF XY:

0.000731

AC XY:

AN XY:

35591

show subpopulations

Gnomad AFR

AF:

0.000319

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000278

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00178

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000755

AC:

138

AN:

182759

Hom.:

AF XY:

0.000683

AC XY:

AN XY:

67397

show subpopulations

Gnomad AFR exome

AF:

0.000381

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.00155

Gnomad OTH exome

AF:

0.000443

GnomAD4 exome

AF:

0.00226

AC:

2482

AN:

1098204

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

780

AN XY:

363566

show subpopulations

Gnomad4 AFR exome

AF:

0.000227

Gnomad4 AMR exome

AF:

0.000170

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.0000993

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.000148

Gnomad4 NFE exome

AF:

0.00287

Gnomad4 OTH exome

AF:

0.000998

GnomAD4 genome

AF:

0.000934

AC:

106

AN:

113518

Hom.:

Cov.:

AF XY:

0.000729

AC XY:

AN XY:

35654

show subpopulations

Gnomad4 AFR

AF:

0.000319

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000279

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00178

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00141

Hom.:

Bravo

AF:

0.000812

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00138

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00178

AC:

ExAC

AF:

0.000684

AC:

EpiCase

AF:

0.00164

EpiControl

AF:

0.00154

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GPRASP2-related disorder

Benign:1

Oct 25, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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

Benign

0.099

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0059

T;T;T

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.80

.;T;.

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;L

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.76

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.039

D;D;D

Sift4G

Benign

0.39

T;T;T

Polyphen

0.94

P;P;P

Vest4

0.22

MVP

0.32

MPC

0.60

ClinPred

0.023

GERP RS

3.9

Varity_R

0.064

gMVP

0.14

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