12-89421159-T-G

Variant summary

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

The NM_172240.3(POC1B):​c.1431A>C​(p.Lys477Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

POC1B
NM_172240.3 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.717
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]

Genome browser will be placed here

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=0.050652325).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
POC1BNM_172240.3 linkc.1431A>C p.Lys477Asn missense_variant 12/12 ENST00000313546.8 NP_758440.1 Q8TC44-1A0MNP0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
POC1BENST00000313546.8 linkc.1431A>C p.Lys477Asn missense_variant 12/121 NM_172240.3 ENSP00000323302.3 Q8TC44-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

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 testingLabcorp Genetics (formerly Invitae), LabcorpNov 15, 2022In 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1503729). This variant has not been reported in the literature in individuals affected with POC1B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 477 of the POC1B protein (p.Lys477Asn). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.014
.;T;.
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.40
FATHMM_MKL
Benign
0.51
D
LIST_S2
Benign
0.51
T;T;T
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.051
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.1
.;M;.
PROVEAN
Benign
0.38
N;N;N
REVEL
Benign
0.022
Sift
Uncertain
0.010
D;D;D
Sift4G
Uncertain
0.030
D;D;D
Polyphen
0.18
.;B;.
Vest4
0.20
MutPred
0.26
.;Loss of methylation at K477 (P = 0.0172);.;
MVP
0.47
MPC
0.13
ClinPred
0.23
T
GERP RS
3.7
Varity_R
0.079
gMVP
0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-89814936; API