rs201784839

Variant names:

• chr12-12942325-C-G
• NM_018654.2:c.899G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-12942325-C-G
• chr12-12942325-C-T

Variant summary

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

The NM_018654.2(GPRC5D):​c.899G>C​(p.Arg300Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GPRC5D NM_018654.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

Genes affected

GPRC5D (HGNC:13310): (G protein-coupled receptor class C group 5 member D) The protein encoded by this gene is a member of the G protein-coupled receptor family; however, the specific function of this gene has not yet been determined. [provided by RefSeq, Jul 2008]

GPRC5D-AS1 (HGNC:53599): (GPRC5D and HEBP1 antisense RNA 1)

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=0.18951988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRC5D	NM_018654.2	c.899G>C	p.Arg300Pro	missense_variant	Exon 3 of 4	ENST00000228887.6	NP_061124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPRC5D	ENST00000228887.6	c.899G>C	p.Arg300Pro	missense_variant	Exon 3 of 4	1	NM_018654.2	ENSP00000228887.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458822 Hom.: 0 Cov.: 28 AF XY: 0.00000276 AC XY: 2 AN XY: 725928

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.073	T
Eigen	Benign	0.031
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.17
Sift	Uncertain	0.021	D
Sift4G	Benign	0.32	T
Polyphen		0.11	B
Vest4		0.42
MutPred		0.34		Loss of stability (P = 0.0141);
MVP		0.36
MPC		0.61
ClinPred		0.93	D
GERP RS		5.9
Varity_R		0.34
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr12-13095259;