chr17-74371783-C-A

Variant names:

• chr17-74371783-C-A
• rs1485335558
• NM_001331076.1:c.308C>A

Variant summary

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

The NM_001331076.1(GPR142):​c.308C>A​(p.Pro103His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. P103L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPR142 NM_001331076.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.71
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR142	NM_001331076.1	c.308C>A	p.Pro103His	missense_variant	Exon 4 of 4	ENST00000582579.6	NP_001318005.1
GPR142	NM_181790.1	c.572C>A	p.Pro191His	missense_variant	Exon 4 of 4		NP_861455.1
GPR142	NM_001331077.1	c.308C>A	p.Pro103His	missense_variant	Exon 4 of 4		NP_001318006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR142	ENST00000582579.6	c.308C>A	p.Pro103His	missense_variant	Exon 4 of 4	1	NM_001331076.1	ENSP00000464632.2
GPR142	ENST00000335666.4	c.572C>A	p.Pro191His	missense_variant	Exon 4 of 4	1		ENSP00000335158.4
GPR142	ENST00000585308.6	c.308C>A	p.Pro103His	missense_variant	Exon 4 of 4	3		ENSP00000463521.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 249752 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.7
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.25
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.67		Loss of glycosylation at P191 (P = 0.0169);
MVP		0.80
MPC		0.58
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.42
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1485335558; hg19: chr17-72367922;