GeneBe

rs201038107

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_148963.4(GPRC6A):​c.2553G>T​(p.Lys851Asn) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

GPRC6A
NM_148963.4 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.503

Publications

1 publications found
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.19013873).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148963.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
GPRC6A
NM_148963.4
MANE Select
c.2553G>Tp.Lys851Asn
missense
Exon 6 of 6NP_683766.2Q5T6X5-1
GPRC6A
NM_001286355.1
c.2340G>Tp.Lys780Asn
missense
Exon 5 of 5NP_001273284.1Q5T6X5-3
GPRC6A
NM_001286354.1
c.2028G>Tp.Lys676Asn
missense
Exon 6 of 6NP_001273283.1Q5T6X5-2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
GPRC6A
ENST00000310357.8
TSL:1 MANE Select
c.2553G>Tp.Lys851Asn
missense
Exon 6 of 6ENSP00000309493.4Q5T6X5-1
GPRC6A
ENST00000368549.7
TSL:1
c.2340G>Tp.Lys780Asn
missense
Exon 5 of 5ENSP00000357537.3Q5T6X5-3
GPRC6A
ENST00000530250.1
TSL:1
c.2028G>Tp.Lys676Asn
missense
Exon 6 of 6ENSP00000433465.1Q5T6X5-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000193
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

ClinVar submissions
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.051
T
Eigen
Benign
-0.40
Eigen_PC
Benign
-0.44
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-0.49
T
MutationAssessor
Benign
0.81
L
PhyloP100
0.50
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.27
Sift
Uncertain
0.010
D
Sift4G
Uncertain
0.0040
D
Polyphen
0.94
P
Vest4
0.090
MutPred
0.46
Loss of ubiquitination at K851 (P = 0.013)
MVP
0.72
MPC
0.13
ClinPred
0.62
D
GERP RS
2.2
Varity_R
0.12
gMVP
0.35
Mutation Taster
=73/27
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs201038107; hg19: chr6-117113533; API