Variant 12-89425162-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_172240.3(POC1B):c.1331A>G(p.Gln444Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

POC1B
NM_172240.3 missense, splice_region

Scores

Splicing: ADA: 0.9972

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.88

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POC1B	NM_172240.3 linkuse as main transcript	c.1331A>G	p.Gln444Arg	missense_variant, splice_region_variant	11/12	ENST00000313546.8	NP_758440.1	Q8TC44-1A0MNP0
POC1B	NM_001199777.2 linkuse as main transcript	c.1205A>G	p.Gln402Arg	missense_variant, splice_region_variant	10/11		NP_001186706.1	Q8TC44-2
POC1B	NR_037659.2 linkuse as main transcript	n.1334A>G		splice_region_variant, non_coding_transcript_exon_variant	11/12
POC1B	NR_037660.2 linkuse as main transcript	n.1370A>G		splice_region_variant, non_coding_transcript_exon_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POC1B	ENST00000313546.8 linkuse as main transcript	c.1331A>G	p.Gln444Arg	missense_variant, splice_region_variant	11/12	1	NM_172240.3	ENSP00000323302.3		Q8TC44-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461606

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727104

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

CeGaT Center for Human Genetics Tuebingen

May 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

0.0068

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

.;T;.

Eigen

Benign

0.17

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.87

D;T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.4

.;M;.

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Benign

0.22

Sift

Benign

0.041

D;D;D

Sift4G

Benign

0.085

T;T;T

Polyphen

0.92

.;P;.

Vest4

0.31

MutPred

0.46

.;Gain of catalytic residue at Q444 (P = 0.009);.;

MVP

0.69

MPC

0.077

ClinPred

0.82

GERP RS

4.6

Varity_R

0.12

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.90

SpliceAI score (max)

0.41

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.41

Position offset: -1

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