13-94612360-C-A

Variant names:

• chr13-94612360-C-A
• NM_180989.6:c.475C>A

Variant summary

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

The NM_180989.6(GPR180):​c.475C>A​(p.Pro159Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPR180 NM_180989.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.51
• Publications: 0 publications found

Genes affected

GPR180 (HGNC:28899): (G protein-coupled receptor 180) This gene encodes a protein that is a member of the G protein-coupled receptor superfamily. This protein is produced predominantly in vascular smooth muscle cells and may play an important role in the regulation of vascular remodeling. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_180989.6. 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
	GPR180	NM_180989.6	MANE Select	c.475C>A	p.Pro159Thr	missense	Exon 3 of 9	NP_851320.1	Q86V85

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR180	ENST00000376958.5	TSL:1 MANE Select	c.475C>A	p.Pro159Thr	missense	Exon 3 of 9	ENSP00000366157.4	Q86V85
	GPR180	ENST00000936762.1		c.394C>A	p.Pro132Thr	missense	Exon 3 of 9	ENSP00000606821.1
	GPR180	ENST00000954032.1		c.475C>A	p.Pro159Thr	missense	Exon 3 of 8	ENSP00000624091.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	Uncertain	0.53
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		6.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.16
Sift	Benign	0.21	T
Sift4G	Uncertain	0.014	D
Polyphen		0.44	B
Vest4		0.76
MutPred		0.56		Gain of catalytic residue at F163 (P = 0.0148)
MVP		0.54
MPC		0.57
ClinPred		0.95	D
GERP RS		5.3
Varity_R		0.19
gMVP		0.65
Mutation Taster		=27/73	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

hg19: chr13-95264614;