NM_080819.5:c.186C>G

Variant names:

• chr4-8581168-C-G
• NM_080819.5:c.186C>G

Variant summary

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

The NM_080819.5(GPR78):​c.186C>G​(p.Phe62Leu) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: GPR78 NM_080819.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.893
• Publications: 0 publications found

Genes affected

GPR78 (HGNC:4528): (G protein-coupled receptor 78) The protein encoded by this gene belongs to the G protein-coupled receptor family, which contain 7 transmembrane domains and transduce extracellular signals through heterotrimeric G proteins. This is an orphan receptor, which displays significant level of constitutive activity. Association analysis shows preliminary evidence for the involvement of this gene in susceptibility to bipolar affective disorder and schizophrenia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2011]

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=0.18819326).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080819.5. 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
	GPR78	NM_080819.5	MANE Select	c.186C>G	p.Phe62Leu	missense	Exon 1 of 3	NP_543009.2
	GPR78	NR_045511.3		n.313+464C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR78	ENST00000382487.5	TSL:1 MANE Select	c.186C>G	p.Phe62Leu	missense	Exon 1 of 3	ENSP00000371927.4	Q96P69
	GPR78	ENST00000509216.1	TSL:1	n.468+464C>G		intron	N/A
	GPR78	ENST00000514302.5	TSL:2	n.186C>G		non_coding_transcript_exon	Exon 2 of 14	ENSP00000424326.1	D6RB95

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 34

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	Pathogenic	0.78
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.2
DANN	Benign	0.54
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.050	N
PhyloP100		0.89
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.059
Sift	Benign	0.74	T
Sift4G	Benign	1.0	T
Polyphen		0.084	B
Vest4		0.020
MutPred		0.35		Loss of catalytic residue at F62 (P = 0.0521)
MVP		0.58
MPC		0.053
ClinPred		0.19	T
GERP RS		1.3
Varity_R		0.11
gMVP		0.24
Mutation Taster		=86/14	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

hg19: chr4-8582895;