Variant chr12-89421219-C-A 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.1371G>T(p.Glu457Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,450,760 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: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

POC1B
NM_172240.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.687

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:

LOC124902981 (HGNC:):

LOC124902981 links:

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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=0.2674694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POC1B	NM_172240.3 link	c.1371G>T	p.Glu457Asp	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 link	c.1371G>T	p.Glu457Asp	missense_variant	12/12	1	NM_172240.3	ENSP00000323302.3		Q8TC44-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247400

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133618

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:

0.00000895

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1450760

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719854

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:

0.00000272

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2024

The c.1371G>T (p.E457D) alteration is located in exon 12 (coding exon 12) of the POC1B gene. This alteration results from a G to T substitution at nucleotide position 1371, causing the glutamic acid (E) at amino acid position 457 to be replaced by an aspartic acid (D). 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

Pathogenic

0.93

BayesDel_addAF

Uncertain

0.046

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

.;D;.

Eigen

Benign

0.10

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.064

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.5

.;M;.

PROVEAN

Uncertain

-2.5

N;D;N

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

0.70

.;P;.

Vest4

0.37

MutPred

0.40

.;Gain of catalytic residue at L453 (P = 0.0174);.;

MVP

0.63

MPC

0.099

ClinPred

0.83

GERP RS

2.4

Varity_R

0.74

gMVP

0.23

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