Variant 6-116792578-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2

The ENST00000310357.8(GPRC6A):c.2345A>G(p.Lys782Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000363 in 1,459,810 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000036 ( 3 hom. )

Consequence

GPRC6A
ENST00000310357.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.955

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GPRC6A	NM_148963.4 linkuse as main transcript	c.2345A>G	p.Lys782Arg	missense_variant	6/6	ENST00000310357.8	NP_683766.2
GPRC6A	NM_001286355.1 linkuse as main transcript	c.2132A>G	p.Lys711Arg	missense_variant	5/5		NP_001273284.1
GPRC6A	NM_001286354.1 linkuse as main transcript	c.1820A>G	p.Lys607Arg	missense_variant	6/6		NP_001273283.1
GPRC6A	XM_017010475.2 linkuse as main transcript	c.2204A>G	p.Lys735Arg	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.2345A>G	p.Lys782Arg	missense_variant	6/6	1	NM_148963.4	ENSP00000309493	P1	Q5T6X5-1
GPRC6A	ENST00000368549.7 linkuse as main transcript	c.2132A>G	p.Lys711Arg	missense_variant	5/5	1		ENSP00000357537		Q5T6X5-3
GPRC6A	ENST00000530250.1 linkuse as main transcript	c.1820A>G	p.Lys607Arg	missense_variant	6/6	1		ENSP00000433465		Q5T6X5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000485

AC:

AN:

247214

Hom.:

AF XY:

0.0000747

AC XY:

AN XY:

133842

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1459810

Hom.:

Cov.:

AF XY:

0.0000496

AC XY:

AN XY:

725856

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000476

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.2345A>G (p.K782R) alteration is located in exon 6 (coding exon 6) of the GPRC6A gene. This alteration results from a A to G substitution at nucleotide position 2345, causing the lysine (K) at amino acid position 782 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Uncertain

0.046

BayesDel_noAF

Uncertain

0.13

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

T;.;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.86

D;T;D

M_CAP

Benign

0.013

MetaRNN

Pathogenic

0.95

D;D;D

MetaSVM

Uncertain

0.54

MutationAssessor

Uncertain

2.2

M;.;.

MutationTaster

Benign

0.98

D;D;N

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.4

N;D;N

REVEL

Pathogenic

0.81

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.15

T;T;T

Polyphen

0.93

P;P;P

Vest4

0.79

MutPred

0.91

Loss of methylation at K782 (P = 0.0069);.;.;

MVP

0.92

MPC

0.17

ClinPred

0.28

GERP RS

4.4

Varity_R

0.20

gMVP

0.70

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