rs774962506
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_006031.6(PCNT):c.4230A>G(p.Glu1410=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
PCNT
NM_006031.6 synonymous
NM_006031.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0490
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
?
Variant 21-46397278-A-G is Benign according to our data. Variant chr21-46397278-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 436194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.049 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCNT | NM_006031.6 | c.4230A>G | p.Glu1410= | synonymous_variant | 22/47 | ENST00000359568.10 | |
PCNT | NM_001315529.2 | c.3876A>G | p.Glu1292= | synonymous_variant | 22/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCNT | ENST00000359568.10 | c.4230A>G | p.Glu1410= | synonymous_variant | 22/47 | 1 | NM_006031.6 | P2 | |
PCNT | ENST00000480896.5 | c.3876A>G | p.Glu1292= | synonymous_variant | 22/47 | 1 | A2 | ||
PCNT | ENST00000695558.1 | c.4263A>G | p.Glu1421= | synonymous_variant | 23/48 | A2 | |||
PCNT | ENST00000703224.1 | c.*3473A>G | 3_prime_UTR_variant, NMD_transcript_variant | 24/49 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
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33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251094Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135766
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461664Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727158
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 29, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 01, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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