chr17-74367690-C-G

Variant names:

• chr17-74367690-C-G
• rs2054991084
• ENST00000335666.4:c.185C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181790.1(GPR142):​c.185C>G​(p.Thr62Arg) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR142 NM_181790.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0340
• Publications: 0 publications found

Genes affected

GPR142 (HGNC:20088): (G protein-coupled receptor 142) GPR142 is a member of the rhodopsin family of G protein-coupled receptors (GPRs) (Fredriksson et al., 2003 [PubMed 14623098]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14283916).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181790.1. 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
	GPR142	NM_001331076.1	MANE Select	c.-178C>G		5_prime_UTR	Exon 1 of 4	NP_001318005.1	Q7Z601
	GPR142	NM_181790.1		c.185C>G	p.Thr62Arg	missense	Exon 1 of 4	NP_861455.1	Q7Z601
	GPR142	NM_001331077.1		c.-132C>G		5_prime_UTR	Exon 1 of 4	NP_001318006.1	Q7Z601

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR142	ENST00000335666.4	TSL:1	c.185C>G	p.Thr62Arg	missense	Exon 1 of 4	ENSP00000335158.4	Q7Z601
	GPR142	ENST00000582579.6	TSL:1 MANE Select	c.-178C>G		5_prime_UTR	Exon 1 of 4	ENSP00000464632.2	J3QSD0
	GPR142	ENST00000585308.6	TSL:3	c.-132C>G		5_prime_UTR	Exon 1 of 4	ENSP00000463521.2	J3QLF2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.074
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	2.7
DANN	Benign	0.94
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.034
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Polyphen		0.64	P
Vest4		0.43
MutPred		0.23		Gain of methylation at T62 (P = 0.0308)
MVP		0.52
MPC		0.18
ClinPred		0.17	T
GERP RS		-3.4
PromoterAI		-0.020	Neutral
Varity_R		0.11
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2054991084; hg19: chr17-72363829;