X-102749947-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001142524.2(GPRASP3):c.952T>C(p.Cys318Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00669 in 1,207,457 control chromosomes in the GnomAD database, including 13 homozygotes. There are 2,590 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0049 ( 1 hom., 163 hem., cov: 23)

Exomes 𝑓: 0.0069 ( 12 hom. 2427 hem. )

Consequence

GPRASP3
NM_001142524.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.66

Variant links:

Genes affected

GPRASP3 (HGNC:29353): (G protein-coupled receptor associated sorting protein family member 3) This gene is a member of a gene family which encodes proteins with a basic helix-loop-helix domain. Other members of this gene family encode proteins which function as transcription factors, either enhancing or inhibiting transcription depending on the activity of other DNA binding proteins. The coding region of this gene is located entirely within the terminal exon. The encoded protein may be involved in the survival of neurons (PMID: 15034937). Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2011]

GPRASP3 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058374703).

BP6

Variant X-102749947-T-C is Benign according to our data. Variant chrX-102749947-T-C is described in ClinVar as [Benign]. Clinvar id is 718264.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-102749947-T-C is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 163 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRASP3	NM_001142524.2 link	c.952T>C	p.Cys318Arg	missense_variant	Exon 4 of 4	ENST00000457056.6	NP_001135996.1	Q6PI77

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPRASP3	ENST00000457056.6 link	c.952T>C	p.Cys318Arg	missense_variant	Exon 4 of 4	4	NM_001142524.2	ENSP00000403226.1		Q6PI77
ARMCX5-GPRASP2	ENST00000652409.1 link	c.952T>C	p.Cys318Arg	missense_variant	Exon 8 of 8			ENSP00000498643.1

Frequencies

GnomAD3 genomes

AF:

0.00488

AC:

547

AN:

112184

Hom.:

Cov.:

AF XY:

0.00475

AC XY:

163

AN XY:

34348

show subpopulations

Gnomad AFR

AF:

0.00107

Gnomad AMI

AF:

0.00875

Gnomad AMR

AF:

0.00197

Gnomad ASJ

AF:

0.00566

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00805

Gnomad MID

AF:

0.00422

Gnomad NFE

AF:

0.00777

Gnomad OTH

AF:

0.00528

GnomAD3 exomes

AF:

0.00489

AC:

877

AN:

179486

Hom.:

AF XY:

0.00457

AC XY:

294

AN XY:

64272

show subpopulations

Gnomad AFR exome

AF:

0.000993

Gnomad AMR exome

AF:

0.00248

Gnomad ASJ exome

AF:

0.00607

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000275

Gnomad FIN exome

AF:

0.00663

Gnomad NFE exome

AF:

0.00776

Gnomad OTH exome

AF:

0.00455

GnomAD4 exome

AF:

0.00687

AC:

7529

AN:

1095217

Hom.:

Cov.:

AF XY:

0.00673

AC XY:

2427

AN XY:

360837

show subpopulations

Gnomad4 AFR exome

AF:

0.000798

Gnomad4 AMR exome

AF:

0.00281

Gnomad4 ASJ exome

AF:

0.00558

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000224

Gnomad4 FIN exome

AF:

0.00706

Gnomad4 NFE exome

AF:

0.00797

Gnomad4 OTH exome

AF:

0.00644

GnomAD4 genome

AF:

0.00487

AC:

547

AN:

112240

Hom.:

Cov.:

AF XY:

0.00474

AC XY:

163

AN XY:

34414

show subpopulations

Gnomad4 AFR

AF:

0.00107

Gnomad4 AMR

AF:

0.00197

Gnomad4 ASJ

AF:

0.00566

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00805

Gnomad4 NFE

AF:

0.00778

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.00722

Hom.:

105

Bravo

AF:

0.00444

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00935

AC:

ESP6500AA

AF:

0.00104

AC:

ESP6500EA

AF:

0.00803

AC:

ExAC

AF:

0.00478

AC:

580

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

T;T;T;T;T

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.61

.;.;.;T;.

MetaRNN

Benign

0.0058

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

M;M;M;M;M

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.1

D;D;D;D;D

REVEL

Benign

0.25

Sift

Benign

0.12

T;T;T;T;T

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

D;D;D;D;D

Vest4

0.48

MVP

0.38

MPC

0.62

ClinPred

0.027

GERP RS

3.5

Varity_R

0.38

gMVP

0.20

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