rs193920808

Variant names:

• chr2-230910022-G-A
• rs193920808
• NM_005683.4:c.941C>T

Variant summary

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

The NM_005683.4(GPR55):​c.941C>T​(p.Thr314Ile) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T314A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR55 NM_005683.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.63
• Publications: 1 publications found

Genes affected

GPR55 (HGNC:4511): (G protein-coupled receptor 55) This gene belongs to the G-protein-coupled receptor superfamily. The encoded integral membrane protein is a likely cannabinoid receptor. It may be involved in several physiological and pathological processes by activating a variety of signal transduction pathways. [provided by RefSeq, Aug 2013]

ENSG00000230385 (HGNC:40260):

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=0.17097384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR55	NM_005683.4	c.941C>T	p.Thr314Ile	missense_variant	Exon 2 of 2	ENST00000650999.1	NP_005674.2
GPR55	XM_005246952.5	c.941C>T	p.Thr314Ile	missense_variant	Exon 2 of 2		XP_005247009.1
GPR55	XM_011512175.4	c.941C>T	p.Thr314Ile	missense_variant	Exon 2 of 2		XP_011510477.1
GPR55	XM_011512176.3	c.941C>T	p.Thr314Ile	missense_variant	Exon 2 of 2		XP_011510478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR55	ENST00000650999.1	c.941C>T	p.Thr314Ile	missense_variant	Exon 2 of 2		NM_005683.4	ENSP00000498258.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer Uncertain:1

-

Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T;T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.50	.;T;.
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;N
PhyloP100		2.6
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.0	.;N;N
REVEL	Benign	0.054
Sift	Uncertain	0.0040	.;D;D
Sift4G	Uncertain	0.031	D;D;D
Polyphen		0.86	P;P;P
Vest4		0.25
MutPred		0.42		Loss of disorder (P = 0.026);Loss of disorder (P = 0.026);Loss of disorder (P = 0.026);
MVP		0.48
MPC		0.64
ClinPred		0.72	D
GERP RS		4.2
Varity_R		0.098
Mutation Taster		=92/8	polymorphism

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

dbSNP: rs193920808; hg19: chr2-231774737; COSMIC: COSV67406963; COSMIC: COSV67406963;