rs587784306
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBS1BS2
The NM_006031.6(PCNT):c.467_505del(p.His156_Gln168del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.018 in 141,884 control chromosomes in the GnomAD database, including 103 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.018 ( 103 hom., cov: 33)
Exomes 𝑓: 0.011 ( 476 hom. )
Failed GnomAD Quality Control
Consequence
PCNT
NM_006031.6 inframe_deletion
NM_006031.6 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.24
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 -14 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_006031.6.
BP6
?
Variant 21-46334557-GTGGGATGTTCACAGTCAGTGACCACCCACCAGAACAGCA-G is Benign according to our data. Variant chr21-46334557-GTGGGATGTTCACAGTCAGTGACCACCCACCAGAACAGCA-G is described in ClinVar as [Likely_benign]. Clinvar id is 159609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46334557-GTGGGATGTTCACAGTCAGTGACCACCCACCAGAACAGCA-G is described in Lovd as [Likely_benign]. Variant chr21-46334557-GTGGGATGTTCACAGTCAGTGACCACCCACCAGAACAGCA-G is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.018 (2549/141884) while in subpopulation NFE AF= 0.0295 (1891/64172). AF 95% confidence interval is 0.0284. There are 103 homozygotes in gnomad4. There are 1147 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 103 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCNT | NM_006031.6 | c.467_505del | p.His156_Gln168del | inframe_deletion | 3/47 | ENST00000359568.10 | |
PCNT | NM_001315529.2 | c.113_151del | p.His38_Gln50del | inframe_deletion | 3/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCNT | ENST00000359568.10 | c.467_505del | p.His156_Gln168del | inframe_deletion | 3/47 | 1 | NM_006031.6 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0180 AC: 2548AN: 141764Hom.: 103 Cov.: 33
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0106 AC: 14627AN: 1376768Hom.: 476 AF XY: 0.0108 AC XY: 7379AN XY: 685088
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome ? AF: 0.0180 AC: 2549AN: 141884Hom.: 103 Cov.: 33 AF XY: 0.0166 AC XY: 1147AN XY: 69254
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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 | May 26, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Microcephalic osteodysplastic primordial dwarfism type II Benign:2
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Feb 22, 2017 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 13, 2013 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at