rs587779355
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_001315529.2(PCNT):c.-159G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Consequence
PCNT
NM_001315529.2 5_prime_UTR_premature_start_codon_gain
NM_001315529.2 5_prime_UTR_premature_start_codon_gain
Scores
2
1
4
Clinical Significance
Conservation
PhyloP100: 1.49
Genes affected
PCNT (HGNC:16068): (pericentrin) The protein encoded by this gene binds to calmodulin and is expressed in the centrosome. It is an integral component of the pericentriolar material (PCM). The protein contains a series of coiled-coil domains and a highly conserved PCM targeting motif called the PACT domain near its C-terminus. The protein interacts with the microtubule nucleation component gamma-tubulin and is likely important to normal functioning of the centrosomes, cytoskeleton, and cell-cycle progression. Mutations in this gene cause Seckel syndrome-4 and microcephalic osteodysplastic primordial dwarfism type II. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
BayesDel_addAF computational evidence supports a deleterious effect, 0.625
PP5
Variant 21-46326518-G-T is Pathogenic according to our data. Variant chr21-46326518-G-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 127247.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr21-46326518-G-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCNT | NM_006031.6 | c.196G>T | p.Gly66* | stop_gained | 2/47 | ENST00000359568.10 | NP_006022.3 | |
PCNT | NM_001315529.2 | c.-159G>T | 5_prime_UTR_premature_start_codon_gain_variant | 2/47 | NP_001302458.1 | |||
PCNT | NM_001315529.2 | c.-159G>T | 5_prime_UTR_variant | 2/47 | NP_001302458.1 | |||
LOC128092249 | NM_001414902.1 | c.*27G>T | downstream_gene_variant | NP_001401831.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCNT | ENST00000359568.10 | c.196G>T | p.Gly66* | stop_gained | 2/47 | 1 | NM_006031.6 | ENSP00000352572.5 | ||
ENSG00000286224 | ENST00000652508.1 | c.*27G>T | downstream_gene_variant | ENSP00000498568.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | - | - - |
Microcephalic osteodysplastic primordial dwarfism type II Pathogenic:1
Pathogenic, flagged submission | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at