Genetic Variant GPR153:p.Gly579Ala (chr1-6249432-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_207370.4(GPR153):c.1736G>C(p.Gly579Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000585 in 1,367,354 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

GPR153
NM_207370.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.168

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.040015876).

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.1736G>C	p.Gly579Ala	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.1736G>C	p.Gly579Ala	missense	Exon 6 of 6	ENSP00000367125.2	Q6NV75
GPR153	ENST00000937750.1		c.1763G>C	p.Gly588Ala	missense	Exon 6 of 6	ENSP00000607809.1
GPR153	ENST00000937749.1		c.1736G>C	p.Gly579Ala	missense	Exon 6 of 6	ENSP00000607808.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151906

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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

GnomAD2 exomes

AF:

0.0000775

AC:

AN:

25804

AF XY:

0.0000640

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000450

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000576

AC:

AN:

1215448

Hom.:

Cov.:

AF XY:

0.00000505

AC XY:

AN XY:

594236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24158

American (AMR)

AF:

0.000506

AC:

AN:

13840

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18216

East Asian (EAS)

AF:

0.00

AC:

AN:

27258

South Asian (SAS)

AF:

0.00

AC:

AN:

52780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3818

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

996736

Other (OTH)

AF:

0.00

AC:

AN:

49538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.404

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151906

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74204

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41432

American (AMR)

AF:

0.0000656

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67914

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.0083

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.50

M_CAP

Benign

0.016

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.17

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.17

REVEL

Benign

0.021

Sift

Benign

0.58

Sift4G

Benign

0.41

Polyphen

0.020

Vest4

0.13

MutPred

0.14

Loss of relative solvent accessibility (P = 0.0071)

MVP

0.11

MPC

0.33

ClinPred

0.033

GERP RS

-0.25

Varity_R

0.089

gMVP

0.29

Mutation Taster

=98/2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over