17-74367706-C-A

Variant names:

• chr17-74367706-C-A
• rs371339688
• ENST00000335666.4:c.201C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181790.1(GPR142):​c.201C>A​(p.Asp67Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPR142 NM_181790.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.42

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=0.10679254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR142	NM_001331076.1	c.-162C>A		5_prime_UTR_variant	Exon 1 of 4	ENST00000582579.6	NP_001318005.1
GPR142	NM_181790.1	c.201C>A	p.Asp67Glu	missense_variant	Exon 1 of 4		NP_861455.1
GPR142	NM_001331077.1	c.-116C>A		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.201C>A	p.Asp67Glu	missense_variant	Exon 1 of 4	1		ENSP00000335158.4
GPR142	ENST00000582579	c.-162C>A		5_prime_UTR_variant	Exon 1 of 4	1	NM_001331076.1	ENSP00000464632.2
GPR142	ENST00000585308	c.-116C>A		5_prime_UTR_variant	Exon 1 of 4	3		ENSP00000463521.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461540 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726976

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 21, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.201C>A (p.D67E) alteration is located in exon 1 (coding exon 1) of the GPR142 gene. This alteration results from a C to A substitution at nucleotide position 201, causing the aspartic acid (D) at amino acid position 67 to be replaced by a glutamic acid (E). 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	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.85
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Polyphen		0.043	B
Vest4		0.19
MutPred		0.22		Gain of sheet (P = 0.0221);
MVP		0.69
MPC		0.12
ClinPred		0.34	T
GERP RS		1.4
Varity_R		0.071
gMVP		0.021

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: rs371339688; hg19: chr17-72363845;