17-74447053-G-T

Position:

• chr17-74447053-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022036.4(GPRC5C):​c.*25G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 1,596,592 control chromosomes in the GnomAD database, including 622,349 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.84 (54781 hom., cov: 34)
  • Exomes 𝑓: 0.89 (567568 hom.)
• Consequence: GPRC5C NM_022036.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.16

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPRC5C	NM_022036.4	c.*25G>T		3_prime_UTR_variant	4/4	ENST00000392627.7	NP_071319.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPRC5C	ENST00000392627.7	c.*25G>T		3_prime_UTR_variant	4/4	1	NM_022036.4	ENSP00000376403	P4

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128525 AN: 152056 Hom.: 54773 Cov.: 34

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.764

Gnomad NFE AF: 0.894

Gnomad OTH AF: 0.850

GnomAD3 exomes AF: 0.876 AC: 215513 AN: 245950 Hom.: 94849 AF XY: 0.874 AC XY: 116453 AN XY: 133202

Gnomad AFR exome AF: 0.715

Gnomad AMR exome AF: 0.934

Gnomad ASJ exome AF: 0.855

Gnomad EAS exome AF: 0.842

Gnomad SAS exome AF: 0.820

Gnomad FIN exome AF: 0.931

Gnomad NFE exome AF: 0.894

Gnomad OTH exome AF: 0.878

GnomAD4 exome AF: 0.886 AC: 1279077 AN: 1444418 Hom.: 567568 Cov.: 46 AF XY: 0.883 AC XY: 631757 AN XY: 715244

Gnomad4 AFR exome AF: 0.719

Gnomad4 AMR exome AF: 0.929

Gnomad4 ASJ exome AF: 0.850

Gnomad4 EAS exome AF: 0.848

Gnomad4 SAS exome AF: 0.823

Gnomad4 FIN exome AF: 0.932

Gnomad4 NFE exome AF: 0.895

Gnomad4 OTH exome AF: 0.868

GnomAD4 genome AF: 0.845 AC: 128570 AN: 152174 Hom.: 54781 Cov.: 34 AF XY: 0.848 AC XY: 63121 AN XY: 74406

Gnomad4 AFR AF: 0.724

Gnomad4 AMR AF: 0.904

Gnomad4 ASJ AF: 0.842

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.824

Gnomad4 FIN AF: 0.932

Gnomad4 NFE AF: 0.894

Gnomad4 OTH AF: 0.845

Alfa AF: 0.867 Hom.: 10438

Bravo AF: 0.836

Asia WGS AF: 0.776 AC: 2701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2706527; hg19: chr17-72443192;