17-74440038-G-A

Variant names:

• chr17-74440038-G-A
• NM_022036.4:c.262G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_022036.4(GPRC5C):​c.262G>A​(p.Gly88Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 4.74
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.828

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.262G>A	p.Gly88Arg	missense	Exon 2 of 4	NP_071319.3
	GPRC5C	NM_001438839.1		c.262G>A	p.Gly88Arg	missense	Exon 2 of 6	NP_001425768.1
	GPRC5C	NM_001366261.2		c.262G>A	p.Gly88Arg	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.262G>A	p.Gly88Arg	missense	Exon 2 of 4	ENSP00000376403.2	Q9NQ84-1
	GPRC5C	ENST00000392629.3	TSL:1	c.262G>A	p.Gly88Arg	missense	Exon 2 of 4	ENSP00000376405.3	Q9NQ84-1
	GPRC5C	ENST00000481232.2	TSL:1	c.262G>A	p.Gly88Arg	missense	Exon 2 of 4	ENSP00000462147.2	Q9BSP0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	28
DANN	Benign	0.97
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	0.68	D
PhyloP100		4.7
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.62
Sift	Benign	0.041	D
Sift4G	Uncertain	0.043	D
Polyphen		0.99	D
Vest4		0.57
MVP		0.78
MPC		1.0
ClinPred		0.96	D
GERP RS		5.7
PromoterAI		0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

hg19: chr17-72436177; COSMIC: COSV61237390; COSMIC: COSV61237390;