X-102715310-G-T

Position:

chrX-102715310-G-T

Variant summary

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

The NM_001004051.4(GPRASP2):c.441G>T(p.Gln147His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000759 in 1,211,615 control chromosomes in the GnomAD database, including 1 homozygotes. There are 40 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: 𝑓 0.000026 ( 0 hom., 1 hem., cov: 25)

Exomes 𝑓: 0.000081 ( 1 hom. 39 hem. )

Consequence

GPRASP2
NM_001004051.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.130

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0116122365).

BS2

High Hemizygotes in GnomAdExome4 at 39 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPRASP2	NM_001004051.4 linkuse as main transcript	c.441G>T	p.Gln147His	missense_variant	5/5	ENST00000483720.7
ARMCX5-GPRASP2	NR_146584.3 linkuse as main transcript	n.795+1044G>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.441G>T	p.Gln147His	missense_variant	5/5	2	NM_001004051.4	P1
ARMCX5-GPRASP2	ENST00000652409.1 linkuse as main transcript	c.-756+1044G>T		intron_variant				P1

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

113387

Hom.:

Cov.:

AF XY:

0.0000282

AC XY:

AN XY:

35513

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000557

Gnomad SAS

AF:

0.000358

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000147

AC:

AN:

183166

Hom.:

AF XY:

0.000222

AC XY:

AN XY:

67620

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00108

Gnomad SAS exome

AF:

0.000525

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000442

GnomAD4 exome

AF:

0.0000810

AC:

AN:

1098177

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

363533

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00215

Gnomad4 SAS exome

AF:

0.000351

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000108

GnomAD4 genome

AF:

0.0000264

AC:

AN:

113438

Hom.:

Cov.:

AF XY:

0.0000281

AC XY:

AN XY:

35574

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000558

Gnomad4 SAS

AF:

0.000359

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.000173

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

Jan 10, 2023

The c.441G>T (p.Q147H) 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 441, causing the glutamine (Q) at amino acid position 147 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

Benign

0.12

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.92

CADD

Benign

9.2

DANN

Benign

0.97

DEOGEN2

Benign

0.075

T;T;T

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.65

.;T;.

M_CAP

Benign

0.0069

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.010

Sift

Uncertain

0.023

D;D;D

Sift4G

Uncertain

0.014

D;D;D

Polyphen

0.0010

B;B;B

Vest4

0.016

MutPred

0.26

Loss of disorder (P = 0.0679);Loss of disorder (P = 0.0679);Loss of disorder (P = 0.0679);

MVP

0.29

MPC

0.13

ClinPred

0.030

GERP RS

-4.3

Varity_R

0.10

gMVP

0.25

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