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GeneBe

12-89425208-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_172240.3(POC1B):c.1285A>G(p.Thr429Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,614,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

POC1B
NM_172240.3 missense

Scores

16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.359
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.011624366).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
POC1BNM_172240.3 linkuse as main transcriptc.1285A>G p.Thr429Ala missense_variant 11/12 ENST00000313546.8
POC1BNM_001199777.2 linkuse as main transcriptc.1159A>G p.Thr387Ala missense_variant 10/11
POC1BNR_037659.2 linkuse as main transcriptn.1288A>G non_coding_transcript_exon_variant 11/12
POC1BNR_037660.2 linkuse as main transcriptn.1324A>G non_coding_transcript_exon_variant 9/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
POC1BENST00000313546.8 linkuse as main transcriptc.1285A>G p.Thr429Ala missense_variant 11/121 NM_172240.3 P1Q8TC44-1

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152206
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000770
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000795
AC:
20
AN:
251416
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135874
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000598
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000575
AC:
84
AN:
1461864
Hom.:
0
Cov.:
31
AF XY:
0.0000619
AC XY:
45
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000353
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000549
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152324
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000771
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000901
Hom.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.0000659
AC:
8
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

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 submitterclinical testingInvitaeJul 26, 2022This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 429 of the POC1B protein (p.Thr429Ala). This variant is present in population databases (rs553428980, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with POC1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1051551). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.67
Cadd
Benign
12
Dann
Benign
0.36
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.073
N
LIST_S2
Benign
0.49
T;T;T
M_CAP
Benign
0.0044
T
MetaRNN
Benign
0.012
T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N;N;N;N
PROVEAN
Benign
0.090
N;N;N
REVEL
Benign
0.014
Sift
Benign
0.90
T;T;T
Sift4G
Benign
0.38
T;T;T
Polyphen
0.0010
.;B;.
Vest4
0.12
MutPred
0.27
.;Gain of catalytic residue at T429 (P = 0.1305);.;
MVP
0.081
MPC
0.059
ClinPred
0.015
T
GERP RS
0.84
Varity_R
0.033
gMVP
0.087

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs553428980; hg19: chr12-89818985; API