12-12913286-T-C

Position:

• chr12-12913286-T-C

Variant summary

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

The ENST00000014914.6(GPRC5A):​c.*747T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,716 control chromosomes in the GnomAD database, including 5,519 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 0.25 (5506 hom., cov: 31)
  • Exomes 𝑓: 0.20 (13 hom.)
• Consequence: GPRC5A ENST00000014914.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143

Genes affected

GPRC5A (HGNC:9836): (G protein-coupled receptor class C group 5 member A) This gene encodes a member of the type 3 G protein-coupling receptor family, characterized by the signature 7-transmembrane domain motif. The encoded protein may be involved in interaction between retinoid acid and G protein signalling pathways. Retinoic acid plays a critical role in development, cellular growth, and differentiation. This gene may play a role in embryonic development and epithelial cell differentiation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPRC5A	NM_003979.4	c.*747T>C		3_prime_UTR_variant	4/4	ENST00000014914.6	NP_003970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPRC5A	ENST00000014914.6	c.*747T>C		3_prime_UTR_variant	4/4	1	NM_003979.4	ENSP00000014914	P1
GPRC5A	ENST00000648791.1	c.*959T>C		3_prime_UTR_variant	3/3			ENSP00000497831
GPRC5A	ENST00000713574.1	c.*747T>C		3_prime_UTR_variant	4/4			ENSP00000518866	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37745 AN: 151916 Hom.: 5486 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.195 AC: 133 AN: 682 Hom.: 13 Cov.: 0 AF XY: 0.199 AC XY: 81 AN XY: 408

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.249 AC: 37797 AN: 152034 Hom.: 5506 Cov.: 31 AF XY: 0.250 AC XY: 18618 AN XY: 74324

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.254

Alfa AF: 0.223 Hom.: 8317

Bravo AF: 0.261

Asia WGS AF: 0.475 AC: 1646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.65

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: rs1061047; hg19: chr12-13066220; COSMIC: COSV50007379; COSMIC: COSV50007379;