chr6-116793029-C-G

Position:

• chr6-116793029-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_148963.4(GPRC6A):​c.1894G>C​(p.Val632Leu) 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. 16/21 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)
• Consequence: GPRC6A NM_148963.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.172

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

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=0.07129595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPRC6A	NM_148963.4	c.1894G>C	p.Val632Leu	missense_variant	6/6	ENST00000310357.8
GPRC6A	NM_001286355.1	c.1681G>C	p.Val561Leu	missense_variant	5/5
GPRC6A	NM_001286354.1	c.1369G>C	p.Val457Leu	missense_variant	6/6
GPRC6A	XM_017010475.2	c.1753G>C	p.Val585Leu	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPRC6A	ENST00000310357.8	c.1894G>C	p.Val632Leu	missense_variant	6/6	1	NM_148963.4	P1
GPRC6A	ENST00000368549.7	c.1681G>C	p.Val561Leu	missense_variant	5/5	1
GPRC6A	ENST00000530250.1	c.1369G>C	p.Val457Leu	missense_variant	6/6	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 03, 2022

The c.1894G>C (p.V632L) alteration is located in exon 6 (coding exon 6) of the GPRC6A gene. This alteration results from a G to C substitution at nucleotide position 1894, causing the valine (V) at amino acid position 632 to be replaced by a leucine (L). 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	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.47
DANN	Benign	0.13
DEOGEN2	Benign	0.10	T;.;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.071	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-2.0	N;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.0	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.88	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0030	B;B;B
Vest4		0.043
MutPred		0.66		Loss of helix (P = 0.1299);.;.;
MVP		0.26
MPC		0.042
ClinPred		0.048	T
GERP RS		-0.60
Varity_R		0.030
gMVP		0.33

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.

Other links and lift over

hg19: chr6-117114192;