Variant chr12-12908793-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003979.4(GPRC5A):c.544A>G(p.Thr182Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00836 in 1,614,018 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0059 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0086 ( 77 hom. )

Consequence

GPRC5A
NM_003979.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.24

Variant links:

Genes affected

GPRC5A (HGNC:9836): (G protein-coupled receptor class C group 5 member A) This gene encodes a member of the type 3 G protein-coupling receptor family, characterized by the signature 7-transmembrane domain motif. The encoded protein may be involved in interaction between retinoid acid and G protein signalling pathways. Retinoic acid plays a critical role in development, cellular growth, and differentiation. This gene may play a role in embryonic development and epithelial cell differentiation. [provided by RefSeq, Jul 2008]

GPRC5A links:

GPRC5A (HGNC:):

GPRC5A 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=0.014664352).

BP6

Variant 12-12908793-A-G is Benign according to our data. Variant chr12-12908793-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2642742.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPRC5A	NM_003979.4 linkuse as main transcript	c.544A>G	p.Thr182Ala	missense_variant	2/4	ENST00000014914.6	NP_003970.1	Q8NFJ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPRC5A	ENST00000014914.6 linkuse as main transcript	c.544A>G	p.Thr182Ala	missense_variant	2/4	1	NM_003979.4	ENSP00000014914.6		Q8NFJ5

Frequencies

GnomAD3 genomes

AF:

0.00593

AC:

902

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00550

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00437

Gnomad FIN

AF:

0.00481

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00931

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00610

AC:

1534

AN:

251400

Hom.:

AF XY:

0.00640

AC XY:

870

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00338

Gnomad ASJ exome

AF:

0.00516

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00686

Gnomad FIN exome

AF:

0.00402

Gnomad NFE exome

AF:

0.00894

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00861

AC:

12591

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00854

AC XY:

6210

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00362

Gnomad4 ASJ exome

AF:

0.00474

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00740

Gnomad4 FIN exome

AF:

0.00389

Gnomad4 NFE exome

AF:

0.00982

Gnomad4 OTH exome

AF:

0.00800

GnomAD4 genome

AF:

0.00593

AC:

903

AN:

152152

Hom.:

Cov.:

AF XY:

0.00619

AC XY:

460

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00188

Gnomad4 AMR

AF:

0.00550

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00437

Gnomad4 FIN

AF:

0.00481

Gnomad4 NFE

AF:

0.00931

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00793

Hom.:

Bravo

AF:

0.00546

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00930

AC:

ExAC

AF:

0.00628

AC:

763

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00971

EpiControl

AF:

0.00895

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

GPRC5A: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

T;T;.

Eigen

Benign

0.012

Eigen_PC

Benign

0.22

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.60

T;T;T

MetaRNN

Benign

0.015

T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

0.97

L;.;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.23

N;N;.

REVEL

Benign

0.26

Sift

Uncertain

0.0010

D;D;.

Sift4G

Uncertain

0.0070

D;D;.

Polyphen

0.010

B;.;.

Vest4

0.26

MVP

0.66

MPC

0.044

ClinPred

0.061

GERP RS

5.4

Varity_R

0.27

gMVP

0.23

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