17-74367690-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 16/21 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR142	NM_001331076.1	c.-178C>G		5_prime_UTR_variant	Exon 1 of 4	ENST00000582579.6	NP_001318005.1
GPR142	NM_181790.1	c.185C>G	p.Thr62Arg	missense_variant	Exon 1 of 4		NP_861455.1
GPR142	NM_001331077.1	c.-132C>G		5_prime_UTR_variant	Exon 1 of 4		NP_001318006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR142	ENST00000335666.4	c.185C>G	p.Thr62Arg	missense_variant	Exon 1 of 4	1		ENSP00000335158.4
GPR142	ENST00000582579	c.-178C>G		5_prime_UTR_variant	Exon 1 of 4	1	NM_001331076.1	ENSP00000464632.2
GPR142	ENST00000585308	c.-132C>G		5_prime_UTR_variant	Exon 1 of 4	3		ENSP00000463521.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.185C>G (p.T62R) alteration is located in exon 1 (coding exon 1) of the GPR142 gene. This alteration results from a C to G substitution at nucleotide position 185, causing the threonine (T) at amino acid position 62 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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
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

Publications

LitVar

Other links and lift over

dbSNP: rs2054991084; hg19: chr17-72363829;