Variant 12-89421235-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_172240.3(POC1B):c.1355G>A(p.Arg452Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000814 in 1,598,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

POC1B
NM_172240.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.31

Variant links:

Genes affected

POC1B (HGNC:30836): (POC1 centriolar protein B) POC1 proteins contain an N-terminal WD40 domain and a C-terminal coiled coil domain and are part of centrosomes. They play an important role in basal body and cilia formation. This gene encodes one of the two POC1 proteins found in humans. Mutation in this gene result in autosomal-recessive cone-rod dystrophy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

POC1B links:

POC1B (HGNC:):

POC1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37996703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POC1B	NM_172240.3 linkuse as main transcript	c.1355G>A	p.Arg452Gln	missense_variant	12/12	ENST00000313546.8	NP_758440.1	Q8TC44-1A0MNP0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POC1B	ENST00000313546.8 linkuse as main transcript	c.1355G>A	p.Arg452Gln	missense_variant	12/12	1	NM_172240.3	ENSP00000323302.3		Q8TC44-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD3 exomes

AF:

0.0000286

AC:

AN:

244738

Hom.:

AF XY:

0.0000227

AC XY:

AN XY:

132142

show subpopulations

Gnomad AFR exome

AF:

0.000259

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0000672

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000692

AC:

AN:

1445878

Hom.:

Cov.:

AF XY:

0.00000697

AC XY:

AN XY:

717272

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000760

Gnomad4 SAS exome

AF:

0.0000354

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000182

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000162

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 11, 2021

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with clinical features of POC1B-related conditions (PMID: 29220607). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs200082142, ExAC 0.01%). This sequence change replaces arginine with glutamine at codon 452 of the POC1B protein (p.Arg452Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.56

.;D;.

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.38

T;T;T

MetaSVM

Uncertain

-0.10

MutationAssessor

Uncertain

2.5

.;M;.

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Uncertain

0.60

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.99

.;D;.

Vest4

0.42

MVP

0.85

MPC

0.32

ClinPred

0.77

GERP RS

5.6

Varity_R

0.77

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over