12-12942280-C-T

Variant names:

• chr12-12942280-C-T
• rs148322311
• NM_018654.2:c.944G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_018654.2(GPRC5D):​c.944G>A​(p.Gly315Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,610,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: GPRC5D NM_018654.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23
• Publications: 4 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3245592).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018654.2. 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
	GPRC5D	NM_018654.2	MANE Select	c.944G>A	p.Gly315Asp	missense	Exon 3 of 4	NP_061124.1	Q9NZD1-1
	GPRC5D-AS1	NR_149062.1		n.78+14477C>T		intron	N/A
	GPRC5D-AS1	NR_149063.1		n.78+14477C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRC5D	ENST00000228887.6	TSL:1 MANE Select	c.944G>A	p.Gly315Asp	missense	Exon 3 of 4	ENSP00000228887.1	Q9NZD1-1
	GPRC5D	ENST00000396333.3	TSL:5	c.896-1431G>A		intron	N/A	ENSP00000379624.3	Q9NZD1-2
	GPRC5D-AS1	ENST00000536029.1	TSL:3	n.40+14477C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152168 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000123 AC: 31 AN: 251358 AF XY: 0.0000957

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000235 AC: 342 AN: 1457998 Hom.: 0 Cov.: 28 AF XY: 0.000219 AC XY: 159 AN XY: 725518

African (AFR) AF: 0.0000299 AC: 1 AN: 33410

American (AMR) AF: 0.000157 AC: 7 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86154

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000294 AC: 326 AN: 1108464

Other (OTH) AF: 0.0000995 AC: 6 AN: 60280

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152286 Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74454

African (AFR) AF: 0.0000241 AC: 1 AN: 41564

American (AMR) AF: 0.000262 AC: 4 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000462 Hom.: 0

Bravo AF: 0.000147

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000115 AC: 14

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000178

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	Benign	0.19
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.2
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.10
Sift	Benign	0.16	T
Sift4G	Benign	0.25	T
Polyphen		1.0	D
Vest4		0.64
MVP		0.20
MPC		0.68
ClinPred		0.52	D
GERP RS		5.6
Varity_R		0.11
gMVP		0.27
Mutation Taster		=84/16	polymorphism

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

dbSNP: rs148322311; hg19: chr12-13095214;