dbSNP rs1382038237: GPR153:p.Gly488Trp (chr1-6249706-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_207370.4(GPR153):c.1462G>T(p.Gly488Trp) 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. 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. G488R) 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: 1.60

Publications

0 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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27729377).

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.1462G>T	p.Gly488Trp	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.1462G>T	p.Gly488Trp	missense	Exon 6 of 6	ENSP00000367125.2	Q6NV75
GPR153	ENST00000937750.1		c.1489G>T	p.Gly497Trp	missense	Exon 6 of 6	ENSP00000607809.1
GPR153	ENST00000937749.1		c.1462G>T	p.Gly488Trp	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:

886418

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

414268

African (AFR)

AF:

0.00

AC:

AN:

16806

American (AMR)

AF:

0.00

AC:

AN:

2844

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6490

East Asian (EAS)

AF:

0.00

AC:

AN:

6156

South Asian (SAS)

AF:

0.00

AC:

AN:

17812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1878

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

797554

Other (OTH)

AF:

0.00

AC:

AN:

30500

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0064

Eigen

Benign

-0.089

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.50

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

1.6

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.77

REVEL

Benign

0.043

Sift

Uncertain

0.016

Sift4G

Uncertain

0.010

Polyphen

0.98

Vest4

0.34

MutPred

0.22

Gain of catalytic residue at P491 (P = 0.0361)

MVP

0.23

MPC

1.0

ClinPred

0.83

GERP RS

1.9

Varity_R

0.22

gMVP

0.43

Mutation Taster

=95/5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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