X-102653934-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001184727.2(GPRASP1):c.21G>C(p.Glu7Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,208,584 control chromosomes in the GnomAD database, including 1 homozygotes. There are 4 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 0.000098 ( 1 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.0000036 ( 0 hom. 0 hem. )

Consequence

GPRASP1
NM_001184727.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.923

Publications

0 publications found

Variant links:

Genes affected

GPRASP1 (HGNC:24834): (G protein-coupled receptor associated sorting protein 1) This gene encodes a member of the GPRASP (G protein-coupled receptor associated sorting protein) family. The protein may modulate lysosomal sorting and functional down-regulation of a variety of G-protein coupled receptors. It targets receptors for degradation in lysosomes. The receptors interacting with this sorting protein include D2 dopamine receptor (DRD2), delta opioid receptor (OPRD1), beta-2 adrenergic receptor (ADRB2), D4 dopamine receptor (DRD4) and cannabinoid 1 receptor (CB1R). Multiple alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, May 2010]

GPRASP1 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:

ENSG00000271147 (HGNC:):

ENSG00000271147 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.041024923).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001184727.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPRASP1	NM_001184727.2	MANE Select	c.21G>C	p.Glu7Asp	missense	Exon 6 of 6	NP_001171656.1	Q5JY77
GPRASP1	NM_001099410.2		c.21G>C	p.Glu7Asp	missense	Exon 4 of 4	NP_001092880.1	Q5JY77
GPRASP1	NM_001099411.2		c.21G>C	p.Glu7Asp	missense	Exon 3 of 3	NP_001092881.1	Q5JY77

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPRASP1	ENST00000537097.2	TSL:2 MANE Select	c.21G>C	p.Glu7Asp	missense	Exon 6 of 6	ENSP00000445683.1	Q5JY77
GPRASP1	ENST00000361600.9	TSL:2	c.21G>C	p.Glu7Asp	missense	Exon 5 of 5	ENSP00000355146.4	Q5JY77
GPRASP1	ENST00000415986.5	TSL:4	c.21G>C	p.Glu7Asp	missense	Exon 4 of 4	ENSP00000393691.1	Q5JY77

Frequencies

GnomAD3 genomes

AF:

0.0000978

AC:

AN:

112503

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000323

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000841

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000661

GnomAD2 exomes

AF:

0.00000551

AC:

AN:

181433

AF XY:

0.0000151

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000368

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000365

AC:

AN:

1096026

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

361498

show subpopulations

African (AFR)

AF:

0.0000380

AC:

AN:

26347

American (AMR)

AF:

0.0000285

AC:

AN:

35105

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19306

East Asian (EAS)

AF:

0.00

AC:

AN:

30194

South Asian (SAS)

AF:

0.00

AC:

AN:

53985

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40511

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4119

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

840448

Other (OTH)

AF:

0.0000435

AC:

AN:

46011

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000977

AC:

AN:

112558

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34718

show subpopulations

African (AFR)

AF:

0.0000323

AC:

AN:

30990

American (AMR)

AF:

0.000840

AC:

AN:

10710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3568

South Asian (SAS)

AF:

0.00

AC:

AN:

2724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6178

Middle Eastern (MID)

AF:

0.00

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53301

Other (OTH)

AF:

0.000653

AC:

AN:

1532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00

Hom.:

Bravo

AF:

0.000219

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.9

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.23

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.56

M_CAP

Benign

0.0055

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PhyloP100

0.92

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-1.4

REVEL

Benign

0.071

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.054

Polyphen

0.80

Vest4

0.090

MutPred

0.12

Gain of catalytic residue at E7 (P = 0.0774)

MVP

0.17

MPC

0.32

ClinPred

0.14

GERP RS

-0.77

Varity_R

0.13

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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