Genetic Variant NM_207370.4:c.1699G>A (chr1-6249469-C-T) – 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.1699G>A(p.Ala567Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000318 in 1,322,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

GPR153
NM_207370.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.804

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:

Genome browser will be placed here

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=0.019772112).

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.1699G>A	p.Ala567Thr	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.1699G>A	p.Ala567Thr	missense	Exon 6 of 6	ENSP00000367125.2	Q6NV75
GPR153	ENST00000937750.1		c.1726G>A	p.Ala576Thr	missense	Exon 6 of 6	ENSP00000607809.1
GPR153	ENST00000937749.1		c.1699G>A	p.Ala567Thr	missense	Exon 6 of 6	ENSP00000607808.1

Frequencies

GnomAD3 genomes

AF:

0.0000857

AC:

AN:

151706

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00251

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:

0.00

AC:

AN:

5250

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000248

AC:

AN:

1170280

Hom.:

Cov.:

AF XY:

0.0000211

AC XY:

AN XY:

568462

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23260

American (AMR)

AF:

0.00

AC:

AN:

9336

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15642

East Asian (EAS)

AF:

0.00109

AC:

AN:

26610

South Asian (SAS)

AF:

0.00

AC:

AN:

43188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26892

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3334

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

974678

Other (OTH)

AF:

0.00

AC:

AN:

47340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000856

AC:

AN:

151814

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41512

American (AMR)

AF:

0.00

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00252

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67886

Other (OTH)

AF:

0.00

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.0000982

ExAC

AF:

0.000111

AC:

Asia WGS

AF:

0.000292

AC:

AN:

3440

ClinVar

ClinVar submissions

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

0.083

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0025

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.42

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.80

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.45

REVEL

Benign

0.030

Sift

Uncertain

0.022

Sift4G

Uncertain

0.032

Polyphen

0.33

Vest4

0.047

MutPred

0.13

Gain of relative solvent accessibility (P = 0.0098)

MVP

0.18

MPC

0.35

ClinPred

0.10

GERP RS

2.8

Varity_R

0.079

gMVP

0.30

Mutation Taster

=97/3

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over