Variant 6-116792887-G-A 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_148963.4(GPRC6A):c.2036C>T(p.Thr679Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,614,062 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 5 hom. )

Consequence

GPRC6A
NM_148963.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.06

Variant links:

Genes affected

GPRC6A (HGNC:18510): (G protein-coupled receptor class C group 6 member A) Members of family C of the G protein-coupled receptor (GPCR) superfamily, such as GPRC6A, are characterized by an evolutionarily conserved amino acid-sensing motif linked to an intramembranous 7-transmembrane loop region. Several members of GPCR family C, including GPRC6A, also have a long N-terminal domain (summary by Pi et al., 2005 [PubMed 16199532]).[supplied by OMIM, Nov 2010]

GPRC6A 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=0.017200917).

BP6

Variant 6-116792887-G-A is Benign according to our data. Variant chr6-116792887-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656867.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GPRC6A	NM_148963.4 linkuse as main transcript	c.2036C>T	p.Thr679Met	missense_variant	6/6	ENST00000310357.8
GPRC6A	NM_001286355.1 linkuse as main transcript	c.1823C>T	p.Thr608Met	missense_variant	5/5
GPRC6A	NM_001286354.1 linkuse as main transcript	c.1511C>T	p.Thr504Met	missense_variant	6/6
GPRC6A	XM_017010475.2 linkuse as main transcript	c.1895C>T	p.Thr632Met	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPRC6A	ENST00000310357.8 linkuse as main transcript	c.2036C>T	p.Thr679Met	missense_variant	6/6	1	NM_148963.4	P1	Q5T6X5-1
GPRC6A	ENST00000368549.7 linkuse as main transcript	c.1823C>T	p.Thr608Met	missense_variant	5/5	1			Q5T6X5-3
GPRC6A	ENST00000530250.1 linkuse as main transcript	c.1511C>T	p.Thr504Met	missense_variant	6/6	1			Q5T6X5-2

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

183

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00222

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00107

AC:

269

AN:

250978

Hom.:

AF XY:

0.00101

AC XY:

137

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000811

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.00185

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00162

AC:

2368

AN:

1461740

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

1104

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.000985

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.000393

Gnomad4 NFE exome

AF:

0.00197

Gnomad4 OTH exome

AF:

0.00124

GnomAD4 genome

AF:

0.00120

AC:

183

AN:

152322

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00222

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00163

Hom.:

Bravo

AF:

0.00110

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.00113

AC:

137

EpiCase

AF:

0.00202

EpiControl

AF:

0.00142

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

Aug 01, 2023

GPRC6A: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

8.3

DANN

Benign

0.83

DEOGEN2

Benign

0.35

T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.62

T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.6

L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

0.0

N;N;N

REVEL

Uncertain

0.30

Sift

Benign

0.25

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.060

B;B;B

Vest4

0.12

MVP

0.64

MPC

0.044

ClinPred

0.0094

GERP RS

-7.9

Varity_R

0.020

gMVP

0.37

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