Variant 6-116792932-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_148963.4(GPRC6A):c.1991C>T(p.Thr664Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GPRC6A
NM_148963.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.98

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16276446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GPRC6A	NM_148963.4 linkuse as main transcript	c.1991C>T	p.Thr664Ile	missense_variant	6/6	ENST00000310357.8	NP_683766.2
GPRC6A	NM_001286355.1 linkuse as main transcript	c.1778C>T	p.Thr593Ile	missense_variant	5/5		NP_001273284.1
GPRC6A	NM_001286354.1 linkuse as main transcript	c.1466C>T	p.Thr489Ile	missense_variant	6/6		NP_001273283.1
GPRC6A	XM_017010475.2 linkuse as main transcript	c.1850C>T	p.Thr617Ile	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.1991C>T	p.Thr664Ile	missense_variant	6/6	1	NM_148963.4	ENSP00000309493	P1	Q5T6X5-1
GPRC6A	ENST00000368549.7 linkuse as main transcript	c.1778C>T	p.Thr593Ile	missense_variant	5/5	1		ENSP00000357537		Q5T6X5-3
GPRC6A	ENST00000530250.1 linkuse as main transcript	c.1466C>T	p.Thr489Ile	missense_variant	6/6	1		ENSP00000433465		Q5T6X5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461748

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727172

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 12, 2023

The c.1991C>T (p.T664I) alteration is located in exon 6 (coding exon 6) of the GPRC6A gene. This alteration results from a C to T substitution at nucleotide position 1991, causing the threonine (T) at amino acid position 664 to be replaced by an isoleucine (I). 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

0.10

BayesDel_addAF

Benign

0.0034

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.17

T;.;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.2

L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.3

N;D;N

REVEL

Uncertain

0.30

Sift

Benign

0.43

T;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.37

B;B;P

Vest4

0.24

MutPred

0.55

Loss of ubiquitination at K660 (P = 0.094);.;.;

MVP

0.64

MPC

0.076

ClinPred

0.14

GERP RS

1.9

Varity_R

0.037

gMVP

0.21

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over