17-74440038-G-A

Position:

• chr17-74440038-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPRC5C	NM_022036.4	c.262G>A	p.Gly88Arg	missense_variant	2/4	ENST00000392627.7	NP_071319.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPRC5C	ENST00000392627.7	c.262G>A	p.Gly88Arg	missense_variant	2/4	1	NM_022036.4	ENSP00000376403.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2024

The c.397G>A (p.G133R) alteration is located in exon 2 (coding exon 2) of the GPRC5C gene. This alteration results from a G to A substitution at nucleotide position 397, causing the glycine (G) at amino acid position 133 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;D;.;D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.83	D;D;D;D
MetaSVM	Uncertain	0.68	D
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.0	.;.;.;D
REVEL	Uncertain	0.62
Sift	Benign	0.041	.;.;.;D
Sift4G	Uncertain	0.043	D;D;D;D
Polyphen		0.99	.;.;.;D
Vest4		0.57, 0.63, 0.58
MVP		0.78
MPC		1.0
ClinPred		0.96	D
GERP RS		5.7
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

Publications

No publications associated with this variant yet.

Other links and lift over

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