Genetic Variant NM_206997.1:c.352G>T (chr11-67452373-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_206997.1(GPR152):c.352G>T(p.Gly118Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,164 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G118S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GPR152
NM_206997.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.542

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

cone-rod synaptic disorder, congenital nonprogressive
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
autosomal dominant nocturnal frontal lobe epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
congenital stationary night blindness
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CABP4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.812

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206997.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR152	NM_206997.1	MANE Select	c.352G>T	p.Gly118Cys	missense	Exon 1 of 1	NP_996880.1	Q8TDT2
CABP4	NM_001300896.3		c.-386C>A		upstream_gene	N/A	NP_001287825.1	P57796-2
CABP4	NM_001379183.1		c.-782C>A		upstream_gene	N/A	NP_001366112.1	P57796-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR152	ENST00000312457.2	TSL:6 MANE Select	c.352G>T	p.Gly118Cys	missense	Exon 1 of 1	ENSP00000310255.2	Q8TDT2
CABP4	ENST00000438189.6	TSL:1	c.-386C>A		upstream_gene	N/A	ENSP00000401555.2	P57796-2
CABP4	ENST00000545040.1	TSL:1	n.-63C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460164

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726460

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52166

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111762

Other (OTH)

AF:

0.00

AC:

AN:

60354

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

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.62

M_CAP

Benign

0.030

MetaRNN

Pathogenic

0.81

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.2

PhyloP100

0.54

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.30

Sift

Uncertain

0.019

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.64

MutPred

0.81

Loss of glycosylation at S117 (P = 0.0459)

MVP

0.67

MPC

0.99

ClinPred

0.98

GERP RS

4.9

PromoterAI

-0.11

Neutral

(source)

Varity_R

0.31

gMVP

0.58

Mutation Taster

=81/19

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