rs17371795
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_006031.6(PCNT):āc.8811A>Gā(p.Thr2937=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,614,024 control chromosomes in the GnomAD database, including 13,937 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.12 ( 1192 hom., cov: 33)
Exomes š: 0.13 ( 12745 hom. )
Consequence
PCNT
NM_006031.6 synonymous
NM_006031.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.80
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
?
Variant 21-46435963-A-G is Benign according to our data. Variant chr21-46435963-A-G is described in ClinVar as [Benign]. Clinvar id is 95343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46435963-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-2.8 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCNT | NM_006031.6 | c.8811A>G | p.Thr2937= | synonymous_variant | 39/47 | ENST00000359568.10 | |
PCNT | NM_001315529.2 | c.8220A>G | p.Thr2740= | synonymous_variant | 39/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCNT | ENST00000359568.10 | c.8811A>G | p.Thr2937= | synonymous_variant | 39/47 | 1 | NM_006031.6 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.118 AC: 18024AN: 152154Hom.: 1193 Cov.: 33
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GnomAD3 exomes AF: 0.142 AC: 35715AN: 251106Hom.: 2820 AF XY: 0.146 AC XY: 19763AN XY: 135768
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GnomAD4 exome AF: 0.127 AC: 185224AN: 1461752Hom.: 12745 Cov.: 34 AF XY: 0.130 AC XY: 94552AN XY: 727192
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GnomAD4 genome ? AF: 0.118 AC: 18044AN: 152272Hom.: 1192 Cov.: 33 AF XY: 0.124 AC XY: 9257AN XY: 74442
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 09, 2013 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Microcephalic osteodysplastic primordial dwarfism type II Benign:1
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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at