Variant chr4-8581178-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_080819.5(GPR78):c.196G>A(p.Gly66Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,602,878 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GPR78
NM_080819.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.89

Variant links:

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]

GPR78 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR78	NM_080819.5 link	c.196G>A	p.Gly66Ser	missense_variant	1/3	ENST00000382487.5	NP_543009.2	Q96P69B2R7M4
GPR78	NR_045511.3 link	n.313+474G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GPR78	ENST00000382487.5 link	c.196G>A	p.Gly66Ser	missense_variant	1/3	1	NM_080819.5	ENSP00000371927.4	Q96P69
GPR78	ENST00000509216.1 link	n.468+474G>A		intron_variant		1
GPR78	ENST00000514302.5 link	n.196G>A		non_coding_transcript_exon_variant	2/14	2		ENSP00000424326.1	D6RB95

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000841

AC:

AN:

237796

Hom.:

AF XY:

0.00000768

AC XY:

AN XY:

130190

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000909

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1450786

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722082

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152092

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 24, 2024

The c.196G>A (p.G66S) alteration is located in exon 1 (coding exon 1) of the GPR78 gene. This alteration results from a G to A substitution at nucleotide position 196, causing the glycine (G) at amino acid position 66 to be replaced by a serine (S). 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

0.32

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.80

M_CAP

Benign

0.0092

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.8

REVEL

Benign

0.19

Sift

Benign

0.18

Sift4G

Uncertain

0.031

Polyphen

1.0

Vest4

0.18

MutPred

0.70

Loss of methylation at R69 (P = 0.0865);

MVP

0.51

MPC

0.18

ClinPred

0.46

GERP RS

2.6

Varity_R

0.15

gMVP

0.38

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over