Genetic Variant GPR153:p.Pro480His (chr1-6249729-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207370.4(GPR153):c.1439C>A(p.Pro480His) 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. 14/22 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. P480S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GPR153
NM_207370.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.636

Publications

2 publications found

Variant links:

Genes affected

GPR153 (HGNC:23618): (G protein-coupled receptor 153) This gene encodes an integral membrane protein that belongs to the Class A rhodopsin superfamily of G protein coupled receptors. The encoded protein is expressed primarily in the central nervous system. A knockdown of the orthologous gene in rat is associated with a significant reduction in food intake and impaired decision making ability. Mutations in this gene are associated with schizophrenia, autism, and other neuropsychiatric disorders. The expression of this gene is activated by the glioma-associated oncogene homolog 1 transcription factor which, in turn, is activated by sonic hedgehog in normal and tumorigenic cells. [provided by RefSeq, Feb 2017]

GPR153 links:

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ACMG classification

Classification was made for transcript

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=0.0680615).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207370.4. 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
	GPR153	NM_207370.4	MANE Select	c.1439C>A	p.Pro480His	missense	Exon 6 of 6	NP_997253.2	A0A0I9QQ03

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR153	ENST00000377893.3	TSL:1 MANE Select	c.1439C>A	p.Pro480His	missense	Exon 6 of 6	ENSP00000367125.2	Q6NV75
GPR153	ENST00000937750.1		c.1466C>A	p.Pro489His	missense	Exon 6 of 6	ENSP00000607809.1
GPR153	ENST00000937749.1		c.1439C>A	p.Pro480His	missense	Exon 6 of 6	ENSP00000607808.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

906940

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

424792

African (AFR)

AF:

0.00

AC:

AN:

17384

American (AMR)

AF:

0.00

AC:

AN:

3370

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7242

East Asian (EAS)

AF:

0.00

AC:

AN:

8232

South Asian (SAS)

AF:

0.00

AC:

AN:

17986

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8484

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1998

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

810560

Other (OTH)

AF:

0.00

AC:

AN:

31684

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0068

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.34

M_CAP

Benign

0.023

MetaRNN

Benign

0.068

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

0.64

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.80

REVEL

Benign

0.053

Sift

Benign

0.039

Sift4G

Uncertain

0.014

Polyphen

0.0010

Vest4

0.15

MutPred

0.20

Loss of catalytic residue at P479 (P = 0.0131)

MVP

0.30

MPC

0.35

ClinPred

0.081

GERP RS

1.5

Varity_R

0.12

gMVP

0.45

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over