Genetic Variant GPR152:p.Ala133Glu (chr11-67452327-G-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_206997.1(GPR152):c.398C>A(p.Ala133Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GPR152
NM_206997.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.551

Variant links:

Genes affected

GPR152 (HGNC:23622): (G protein-coupled receptor 152) Enables identical protein binding activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR152 links:

CABP4 (HGNC:1386): (calcium binding protein 4) This gene encodes a member of the CABP family of calcium binding protein characterized by four EF-hand motifs. Mutations in this gene are associated with congenital stationary night blindness type 2B. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

CABP4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.77

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR152	NM_206997.1 link	c.398C>A	p.Ala133Glu	missense_variant	Exon 1 of 1	ENST00000312457.2	NP_996880.1	Q8TDT2A0A0I9RJ67
CABP4	NM_001300896.3 link	c.-432G>T		upstream_gene_variant			NP_001287825.1	P57796-2A0A024R5K4
CABP4	NM_001379183.1 link	c.-828G>T		upstream_gene_variant			NP_001366112.1
CABP4	XM_024448615.2 link	c.-3006G>T		upstream_gene_variant			XP_024304383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR152	ENST00000312457.2 link	c.398C>A	p.Ala133Glu	missense_variant	Exon 1 of 1	6	NM_206997.1	ENSP00000310255.2		Q8TDT2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000413

AC:

AN:

242308

Hom.:

AF XY:

0.00000755

AC XY:

AN XY:

132506

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000922

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458532

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725760

show subpopulations

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.13

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

Eigen

Benign

0.023

Eigen_PC

Benign

0.064

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.69

M_CAP

Benign

0.072

MetaRNN

Pathogenic

0.77

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.52

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0

Polyphen

0.66

Vest4

0.78

MutPred

0.70

Gain of helix (P = 0.1736);

MVP

0.77

MPC

1.0

ClinPred

0.91

GERP RS

3.5

Varity_R

0.34

gMVP

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over