Variant chr6-116792761-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_148963.4(GPRC6A):c.2162T>C(p.Leu721Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

GPRC6A
NM_148963.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.702

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41424617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GPRC6A	NM_148963.4 linkuse as main transcript	c.2162T>C	p.Leu721Pro	missense_variant	6/6	ENST00000310357.8
GPRC6A	NM_001286355.1 linkuse as main transcript	c.1949T>C	p.Leu650Pro	missense_variant	5/5
GPRC6A	NM_001286354.1 linkuse as main transcript	c.1637T>C	p.Leu546Pro	missense_variant	6/6
GPRC6A	XM_017010475.2 linkuse as main transcript	c.2021T>C	p.Leu674Pro	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPRC6A	ENST00000310357.8 linkuse as main transcript	c.2162T>C	p.Leu721Pro	missense_variant	6/6	1	NM_148963.4	P1	Q5T6X5-1
GPRC6A	ENST00000368549.7 linkuse as main transcript	c.1949T>C	p.Leu650Pro	missense_variant	5/5	1			Q5T6X5-3
GPRC6A	ENST00000530250.1 linkuse as main transcript	c.1637T>C	p.Leu546Pro	missense_variant	6/6	1			Q5T6X5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

250814

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135536

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461706

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000247

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

Jan 30, 2024

The c.2162T>C (p.L721P) alteration is located in exon 6 (coding exon 6) of the GPRC6A gene. This alteration results from a T to C substitution at nucleotide position 2162, causing the leucine (L) at amino acid position 721 to be replaced by a proline (P). 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

0.30

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

D;.;.

Eigen

Benign

0.13

Eigen_PC

Benign

-0.035

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.41

T;T;T

MetaSVM

Uncertain

0.026

MutationAssessor

Uncertain

2.8

M;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Uncertain

0.62

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.015

D;D;D

Polyphen

0.98

D;P;D

Vest4

0.44

MutPred

0.69

Loss of stability (P = 0.0083);.;.;

MVP

0.77

MPC

0.30

ClinPred

0.76

GERP RS

4.4

Varity_R

0.75

gMVP

0.77

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