rs143005344

Variant names:

• chr12-12908494-C-A
• rs143005344
• NM_003979.4:c.245C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-12908494-C-A
• chr12-12908494-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003979.4(GPRC5A):​c.245C>A​(p.Thr82Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T82I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GPRC5A NM_003979.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.92
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.757

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRC5A	NM_003979.4	c.245C>A	p.Thr82Asn	missense_variant	Exon 2 of 4	ENST00000014914.6	NP_003970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPRC5A	ENST00000014914.6	c.245C>A	p.Thr82Asn	missense_variant	Exon 2 of 4	1	NM_003979.4	ENSP00000014914.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461828 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727206

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.81	D;D;.
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.76	D;D;D
MetaSVM	Uncertain	0.70	D
MutationAssessor	Pathogenic	3.3	M;.;.
PhyloP100		4.9
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-4.1	D;D;.
REVEL	Uncertain	0.58
Sift	Uncertain	0.0020	D;D;.
Sift4G	Uncertain	0.0020	D;D;.
Polyphen		1.0	D;.;.
Vest4		0.70
MutPred		0.52		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.90
MPC		0.28
ClinPred		0.99	D
GERP RS		5.6
PromoterAI		0.049	Neutral
Varity_R		0.73
gMVP		0.82
Mutation Taster		=31/69	disease causing

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

Other links and lift over

dbSNP: rs143005344; hg19: chr12-13061428;