Genetic Variant NM_207370.4:c.1567C>T (chr1-6249601-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207370.4(GPR153):c.1567C>T(p.Pro523Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.50

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.054397225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR153	NM_207370.4 link	c.1567C>T	p.Pro523Ser	missense_variant	Exon 6 of 6	ENST00000377893.3	NP_997253.2
GPR153	XM_011541434.4 link	c.1567C>T	p.Pro523Ser	missense_variant	Exon 6 of 6		XP_011539736.1	Q6NV75A0A0I9QQ03
GPR153	XM_017001250.2 link	c.1567C>T	p.Pro523Ser	missense_variant	Exon 5 of 5		XP_016856739.1	Q6NV75A0A0I9QQ03

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR153	ENST00000377893.3 link	c.1567C>T	p.Pro523Ser	missense_variant	Exon 6 of 6	1	NM_207370.4	ENSP00000367125.2		Q6NV75

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

996700

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

468984

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 07, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1567C>T (p.P523S) alteration is located in exon 6 (coding exon 5) of the GPR153 gene. This alteration results from a C to T substitution at nucleotide position 1567, causing the proline (P) at amino acid position 523 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0038

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.36

M_CAP

Benign

0.013

MetaRNN

Benign

0.054

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.37

REVEL

Benign

0.072

Sift

Benign

0.63

Sift4G

Benign

0.81

Polyphen

0.039

Vest4

0.052

MutPred

0.14

Gain of phosphorylation at P523 (P = 0.0205);

MVP

0.14

MPC

0.31

ClinPred

0.073

GERP RS

2.6

Varity_R

0.055

gMVP

0.51

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over