4-8581340-C-A

Variant names:

• chr4-8581340-C-A
• NM_080819.5:c.358C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080819.5(GPR78):​c.358C>A​(p.Pro120Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,423,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. P120S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GPR78 NM_080819.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19598848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR78	NM_080819.5	c.358C>A	p.Pro120Thr	missense_variant	Exon 1 of 3	ENST00000382487.5	NP_543009.2
GPR78	NR_045511.3	n.313+636C>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR78	ENST00000382487.5	c.358C>A	p.Pro120Thr	missense_variant	Exon 1 of 3	1	NM_080819.5	ENSP00000371927.4
GPR78	ENST00000509216.1	n.468+636C>A		intron_variant	Intron 1 of 2	1
GPR78	ENST00000514302.5	n.358C>A		non_coding_transcript_exon_variant	Exon 2 of 14	2		ENSP00000424326.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1423444 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 705476

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.69	N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.13
Sift	Benign	0.39	T
Sift4G	Benign	0.38	T
Polyphen		0.96	D
Vest4		0.087
MutPred		0.38		Loss of glycosylation at P120 (P = 0.0314);
MVP		0.79
MPC		0.16
ClinPred		0.39	T
GERP RS		-0.51
Varity_R		0.073
gMVP		0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-8583067;