NM_018654.2:c.899G>C

Variant names:

• chr12-12942325-C-G
• rs201784839
• NM_018654.2:c.899G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R300Q) has been classified as Uncertain significance.

• 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
• Publications: 0 publications found

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

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=0.18951988).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018654.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRC5D	NM_018654.2	MANE Select	c.899G>C	p.Arg300Pro	missense	Exon 3 of 4	NP_061124.1	Q9NZD1-1
	GPRC5D-AS1	NR_149062.1		n.78+14522C>G		intron	N/A
	GPRC5D-AS1	NR_149063.1		n.78+14522C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRC5D	ENST00000228887.6	TSL:1 MANE Select	c.899G>C	p.Arg300Pro	missense	Exon 3 of 4	ENSP00000228887.1	Q9NZD1-1
	GPRC5D	ENST00000396333.3	TSL:5	c.896-1476G>C		intron	N/A	ENSP00000379624.3	Q9NZD1-2
	GPRC5D-AS1	ENST00000536029.1	TSL:3	n.40+14522C>G		intron	N/A

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

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109268

Other (OTH) AF: 0.00 AC: 0 AN: 60278

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.6
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
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs201784839; hg19: chr12-13095259;