rs10222116
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_006031.6(PCNT):c.6150+11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,414,308 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 14 hom., cov: 33)
Exomes 𝑓: 0.0010 ( 11 hom. )
Failed GnomAD Quality Control
Consequence
PCNT
NM_006031.6 intron
NM_006031.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.316
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 21-46413003-G-C is Benign according to our data. Variant chr21-46413003-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 159629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46413003-G-C is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00103 (1455/1414308) while in subpopulation AFR AF= 0.0135 (428/31758). AF 95% confidence interval is 0.0124. There are 11 homozygotes in gnomad4_exome. There are 718 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 11 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCNT | NM_006031.6 | c.6150+11G>C | intron_variant | ENST00000359568.10 | |||
PCNT | NM_001315529.2 | c.5796+11G>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCNT | ENST00000359568.10 | c.6150+11G>C | intron_variant | 1 | NM_006031.6 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0123 AC: 1466AN: 119418Hom.: 14 Cov.: 33
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GnomAD3 exomes AF: 0.00425 AC: 941AN: 221224Hom.: 10 AF XY: 0.00354 AC XY: 426AN XY: 120238
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GnomAD4 exome AF: 0.00103 AC: 1455AN: 1414308Hom.: 11 Cov.: 33 AF XY: 0.00102 AC XY: 718AN XY: 703536
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.0123 AC: 1471AN: 119518Hom.: 14 Cov.: 33 AF XY: 0.0121 AC XY: 708AN XY: 58376
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Microcephalic osteodysplastic primordial dwarfism type II Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 02, 2020 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 25, 2013 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at