6-116809541-G-C

Variant names:

• chr6-116809541-G-C
• rs2274911
• NM_148963.4:c.271C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_148963.4(GPRC6A):​c.271C>G​(p.Pro91Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPRC6A NM_148963.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.315
• Publications: 50 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2347745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRC6A	NM_148963.4	c.271C>G	p.Pro91Ala	missense_variant	Exon 2 of 6	ENST00000310357.8	NP_683766.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPRC6A	ENST00000310357.8	c.271C>G	p.Pro91Ala	missense_variant	Exon 2 of 6	1	NM_148963.4	ENSP00000309493.4
GPRC6A	ENST00000368549.7	c.271C>G	p.Pro91Ala	missense_variant	Exon 2 of 5	1		ENSP00000357537.3
GPRC6A	ENST00000530250.1	c.271C>G	p.Pro91Ala	missense_variant	Exon 2 of 6	1		ENSP00000433465.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Uncertain	0.56	D;.;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.54	T;T;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.6	M;M;M
PhyloP100		0.32
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-4.8	D;D;D
REVEL	Uncertain	0.30
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.13	B;B;B
Vest4		0.19
MutPred		0.65		Gain of catalytic residue at P91 (P = 0.0277);Gain of catalytic residue at P91 (P = 0.0277);Gain of catalytic residue at P91 (P = 0.0277);
MVP		0.63
MPC		0.057
ClinPred		0.61	D
GERP RS		-0.33
Varity_R		0.12
gMVP		0.34
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs2274911; hg19: chr6-117130704;