Variant 6-116792269-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000310357.8(GPRC6A):c.2654C>A(p.Ser885Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00339 in 1,614,036 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 23 hom. )

Consequence

GPRC6A
ENST00000310357.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.319

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=0.004604399).

BP6

Variant 6-116792269-G-T is Benign according to our data. Variant chr6-116792269-G-T is described in ClinVar as [Benign]. Clinvar id is 777626.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GPRC6A	NM_148963.4 linkuse as main transcript	c.2654C>A	p.Ser885Tyr	missense_variant	6/6	ENST00000310357.8	NP_683766.2
GPRC6A	NM_001286355.1 linkuse as main transcript	c.2441C>A	p.Ser814Tyr	missense_variant	5/5		NP_001273284.1
GPRC6A	NM_001286354.1 linkuse as main transcript	c.2129C>A	p.Ser710Tyr	missense_variant	6/6		NP_001273283.1
GPRC6A	XM_017010475.2 linkuse as main transcript	c.2513C>A	p.Ser838Tyr	missense_variant	7/7		XP_016865964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPRC6A	ENST00000310357.8 linkuse as main transcript	c.2654C>A	p.Ser885Tyr	missense_variant	6/6	1	NM_148963.4	ENSP00000309493	P1	Q5T6X5-1
GPRC6A	ENST00000368549.7 linkuse as main transcript	c.2441C>A	p.Ser814Tyr	missense_variant	5/5	1		ENSP00000357537		Q5T6X5-3
GPRC6A	ENST00000530250.1 linkuse as main transcript	c.2129C>A	p.Ser710Tyr	missense_variant	6/6	1		ENSP00000433465		Q5T6X5-2

Frequencies

GnomAD3 genomes

AF:

0.00341

AC:

519

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.0256

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00316

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00387

AC:

971

AN:

250942

Hom.:

AF XY:

0.00399

AC XY:

541

AN XY:

135604

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000947

Gnomad FIN exome

AF:

0.0244

Gnomad NFE exome

AF:

0.00333

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00338

AC:

4947

AN:

1461766

Hom.:

Cov.:

AF XY:

0.00333

AC XY:

2420

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00103

Gnomad4 FIN exome

AF:

0.0212

Gnomad4 NFE exome

AF:

0.00319

Gnomad4 OTH exome

AF:

0.00219

GnomAD4 genome

AF:

0.00341

AC:

519

AN:

152270

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

333

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0256

Gnomad4 NFE

AF:

0.00316

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00290

Hom.:

Bravo

AF:

0.00141

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00343

AC:

416

EpiCase

AF:

0.00235

EpiControl

AF:

0.00225

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Benign

6.5

DANN

Benign

0.19

DEOGEN2

Benign

0.073

T;.;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.73

T;T;T

MetaRNN

Benign

0.0046

T;T;T

MetaSVM

Benign

-0.44

MutationAssessor

Benign

0.55

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.093

Sift

Uncertain

0.022

D;D;D

Sift4G

Uncertain

0.024

D;D;D

Polyphen

0.15

B;B;B

Vest4

0.15

MVP

0.84

MPC

0.086

ClinPred

0.0096

GERP RS

2.5

Varity_R

0.045

gMVP

0.32

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