chr17-74440411-C-G

Variant names:

• chr17-74440411-C-G
• rs2055513324
• NM_022036.4:c.635C>G

Variant summary

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

The NM_022036.4(GPRC5C):​c.635C>G​(p.Ala212Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPRC5C NM_022036.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.95
• 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.635C>G	p.Ala212Gly	missense	Exon 2 of 4	NP_071319.3
	GPRC5C	NM_001438839.1		c.635C>G	p.Ala212Gly	missense	Exon 2 of 6	NP_001425768.1
	GPRC5C	NM_001366261.2		c.635C>G	p.Ala212Gly	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.635C>G	p.Ala212Gly	missense	Exon 2 of 4	ENSP00000376403.2	Q9NQ84-1
	GPRC5C	ENST00000392629.3	TSL:1	c.635C>G	p.Ala212Gly	missense	Exon 2 of 4	ENSP00000376405.3	Q9NQ84-1
	GPRC5C	ENST00000481232.2	TSL:1	c.270+365C>G		intron	N/A	ENSP00000462147.2	Q9BSP0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	0.69	D
PhyloP100		4.9
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.3	D
REVEL	Pathogenic	0.65
Sift	Benign	0.030	D
Sift4G	Uncertain	0.020	D
Polyphen		0.97	D
Vest4		0.64
MVP		0.82
MPC		0.90
ClinPred		0.99	D
GERP RS		5.8

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: rs2055513324; hg19: chr17-72436550;