12-12949576-C-T

Position:

• chr12-12949576-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000228887.6(GPRC5D):​c.809G>A​(p.Arg270Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPRC5D ENST00000228887.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.336

Genes affected

GPRC5D (HGNC:13310): (G protein-coupled receptor class C group 5 member D) The protein encoded by this gene is a member of the G protein-coupled receptor family; however, the specific function of this gene has not yet been determined. [provided by RefSeq, Jul 2008]

GPRC5D-AS1 (HGNC:53599): (GPRC5D and HEBP1 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040874183).
• BP6: Variant 12-12949576-C-T is Benign according to our data. Variant chr12-12949576-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2246125.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPRC5D	NM_018654.2	c.809G>A	p.Arg270Lys	missense_variant	2/4	ENST00000228887.6	NP_061124.1
GPRC5D-AS1	NR_149067.1	n.78+21773C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPRC5D	ENST00000228887.6	c.809G>A	p.Arg270Lys	missense_variant	2/4	1	NM_018654.2	ENSP00000228887	P4
GPRC5D-AS1	ENST00000542078.2	n.70+21773C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.034
DANN	Benign	0.78
DEOGEN2	Benign	0.0039	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.50	T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.42	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.55	N;N
REVEL	Benign	0.021
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.060
MutPred		0.44		Gain of catalytic residue at Y266 (P = 9e-04);Gain of catalytic residue at Y266 (P = 9e-04);
MVP		0.12
MPC		0.16
ClinPred		0.077	T
GERP RS		-7.0
Varity_R		0.039
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-13102510;