X-102715195-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R109C) has been classified as Uncertain significance.

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

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3053315.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 26 Unknown,XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004051.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPRASP2	NM_001004051.4	MANE Select	c.326G>A	p.Arg109His	missense	Exon 5 of 5	NP_001004051.1	Q96D09
GPRASP2	NM_001184874.3		c.326G>A	p.Arg109His	missense	Exon 5 of 5	NP_001171803.1	Q96D09
GPRASP2	NM_001184875.3		c.326G>A	p.Arg109His	missense	Exon 4 of 4	NP_001171804.1	Q96D09

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPRASP2	ENST00000483720.7	TSL:2 MANE Select	c.326G>A	p.Arg109His	missense	Exon 5 of 5	ENSP00000507692.1	Q96D09
GPRASP2	ENST00000332262.10	TSL:1	c.326G>A	p.Arg109His	missense	Exon 4 of 4	ENSP00000339057.3	Q96D09
ARMCX5-GPRASP2	ENST00000652409.1		c.-756+929G>A		intron	N/A	ENSP00000498643.1

Frequencies

GnomAD3 genomes

AF:

0.000934

AC:

106

AN:

113465

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000755

AC:

138

AN:

182759

AF XY:

0.000683

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 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

African (AFR)

AF:

0.000227

AC:

AN:

26403

American (AMR)

AF:

0.000170

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.0000516

AC:

AN:

19386

East Asian (EAS)

AF:

0.0000993

AC:

AN:

30206

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54149

European-Finnish (FIN)

AF:

0.000148

AC:

AN:

40493

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00287

AC:

2413

AN:

842127

Other (OTH)

AF:

0.000998

AC:

AN:

46096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

134

268

403

537

671

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000934

AC:

106

AN:

113518

Hom.:

Cov.:

AF XY:

0.000729

AC XY:

AN XY:

35654

show subpopulations

African (AFR)

AF:

0.000319

AC:

AN:

31385

American (AMR)

AF:

0.00

AC:

AN:

10872

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2662

East Asian (EAS)

AF:

0.000279

AC:

AN:

3585

South Asian (SAS)

AF:

0.00

AC:

AN:

2809

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6333

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00178

AC:

AN:

53423

Other (OTH)

AF:

0.00

AC:

AN:

1543

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00133

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

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

GPRASP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0059

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.80

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

2.6

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.76

REVEL

Benign

0.11

Sift

Benign

0.039

Sift4G

Benign

0.39

Polyphen

0.94

Vest4

0.22

MVP

0.32

MPC

0.60

ClinPred

0.023

GERP RS

3.9

Varity_R

0.064

gMVP

0.14

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over