rs1229179337

Variant names:

• chr17-74440230-C-G
• rs1229179337
• NM_022036.4:c.454C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-74440230-C-G
• chr17-74440230-C-T

Variant summary

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

The NM_022036.4(GPRC5C):​c.454C>G​(p.Arg152Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. 11/19 in silico tools predict 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. R152W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPRC5C NM_022036.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24
• Publications: 0 publications found

Genes affected

GPRC5C (HGNC:13309): (G protein-coupled receptor class C group 5 member C) The protein encoded by this gene is a member of the type 3 G protein-coupled receptor family. Members of this superfamily are characterized by a signature 7-transmembrane domain motif. The specific function of this protein is unknown; however, this protein may mediate the cellular effects of retinoic acid on the G protein signal transduction cascade. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022036.4. 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
	GPRC5C	NM_022036.4	MANE Select	c.454C>G	p.Arg152Gly	missense	Exon 2 of 4	NP_071319.3
	GPRC5C	NM_001438839.1		c.454C>G	p.Arg152Gly	missense	Exon 2 of 6	NP_001425768.1
	GPRC5C	NM_001366261.2		c.454C>G	p.Arg152Gly	missense	Exon 2 of 5	NP_001353190.1	A8MXZ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRC5C	ENST00000392627.7	TSL:1 MANE Select	c.454C>G	p.Arg152Gly	missense	Exon 2 of 4	ENSP00000376403.2	Q9NQ84-1
	GPRC5C	ENST00000392629.3	TSL:1	c.454C>G	p.Arg152Gly	missense	Exon 2 of 4	ENSP00000376405.3	Q9NQ84-1
	GPRC5C	ENST00000481232.2	TSL:1	c.270+184C>G		intron	N/A	ENSP00000462147.2	Q9BSP0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	22
DANN	Benign	0.97
Eigen	Benign	0.031
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	-0.034	T
PhyloP100		2.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.37
Sift	Benign	0.54	T
Sift4G	Benign	0.55	T
Polyphen		0.38	B
Vest4		0.59
MVP		0.66
MPC		0.34
ClinPred		0.69	D
GERP RS		4.6
PromoterAI		-0.0096	Neutral

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: rs1229179337; hg19: chr17-72436369;