Genetic Variant NM_207370.4:c.1480G>T (chr1-6249688-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207370.4(GPR153):c.1480G>T(p.Ala494Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000554 in 902,926 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A494T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

GPR153
NM_207370.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.612

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0379214).

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.1480G>T	p.Ala494Ser	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.1480G>T	p.Ala494Ser	missense	Exon 6 of 6	ENSP00000367125.2	Q6NV75
GPR153	ENST00000937750.1		c.1507G>T	p.Ala503Ser	missense	Exon 6 of 6	ENSP00000607809.1
GPR153	ENST00000937749.1		c.1480G>T	p.Ala494Ser	missense	Exon 6 of 6	ENSP00000607808.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000554

AC:

AN:

902926

Hom.:

Cov.:

AF XY:

0.00000946

AC XY:

AN XY:

422632

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17232

American (AMR)

AF:

0.00

AC:

AN:

3252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7094

East Asian (EAS)

AF:

0.00

AC:

AN:

7812

South Asian (SAS)

AF:

0.00

AC:

AN:

17974

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8312

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1962

European-Non Finnish (NFE)

AF:

0.00000619

AC:

AN:

807846

Other (OTH)

AF:

0.00

AC:

AN:

31442

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.565

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

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

0.083

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0021

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.50

M_CAP

Benign

0.073

MetaRNN

Benign

0.038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

0.61

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.15

REVEL

Benign

0.038

Sift

Benign

0.51

Sift4G

Benign

0.66

Polyphen

0.0040

Vest4

0.12

MutPred

0.20

Gain of phosphorylation at A494 (P = 0.0024)

MVP

0.15

MPC

0.43

ClinPred

0.14

GERP RS

3.0

Varity_R

0.077

gMVP

0.40

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over