rs80017051

Positions:

chr21-46324288-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006031.6(PCNT):c.54+6C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0553 in 1,605,538 control chromosomes in the GnomAD database, including 2,873 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 211 hom., cov: 35)

Exomes 𝑓: 0.057 ( 2662 hom. )

Consequence

PCNT
NM_006031.6 splice_donor_region, intron

Scores

Splicing: ADA: 0.00008184

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.315

Variant links:

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]

PCNT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 21-46324288-C-T is Benign according to our data. Variant chr21-46324288-C-T is described in ClinVar as [Benign]. Clinvar id is 138618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46324288-C-T is described in Lovd as [Benign]. Variant chr21-46324288-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCNT	NM_006031.6 linkuse as main transcript	c.54+6C>T		splice_donor_region_variant, intron_variant		ENST00000359568.10	NP_006022.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCNT	ENST00000359568.10 linkuse as main transcript	c.54+6C>T		splice_donor_region_variant, intron_variant		1	NM_006031.6	ENSP00000352572	P2	O95613-1

Frequencies

GnomAD3 genomes

AF:

0.0432

AC:

6572

AN:

152208

Hom.:

212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.0275

Gnomad AMR

AF:

0.0263

Gnomad ASJ

AF:

0.0559

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00889

Gnomad FIN

AF:

0.0858

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0660

Gnomad OTH

AF:

0.0401

GnomAD3 exomes

AF:

0.0443

AC:

10466

AN:

236278

Hom.:

276

AF XY:

0.0443

AC XY:

5680

AN XY:

128314

show subpopulations

Gnomad AFR exome

AF:

0.00854

Gnomad AMR exome

AF:

0.0185

Gnomad ASJ exome

AF:

0.0566

Gnomad EAS exome

AF:

0.0000563

Gnomad SAS exome

AF:

0.0137

Gnomad FIN exome

AF:

0.0869

Gnomad NFE exome

AF:

0.0641

Gnomad OTH exome

AF:

0.0475

GnomAD4 exome

AF:

0.0566

AC:

82288

AN:

1453214

Hom.:

2662

Cov.:

AF XY:

0.0555

AC XY:

40141

AN XY:

722714

show subpopulations

Gnomad4 AFR exome

AF:

0.00825

Gnomad4 AMR exome

AF:

0.0205

Gnomad4 ASJ exome

AF:

0.0552

Gnomad4 EAS exome

AF:

0.0000760

Gnomad4 SAS exome

AF:

0.0134

Gnomad4 FIN exome

AF:

0.0854

Gnomad4 NFE exome

AF:

0.0641

Gnomad4 OTH exome

AF:

0.0498

GnomAD4 genome

AF:

0.0431

AC:

6570

AN:

152324

Hom.:

211

Cov.:

AF XY:

0.0423

AC XY:

3149

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.0262

Gnomad4 ASJ

AF:

0.0559

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00910

Gnomad4 FIN

AF:

0.0858

Gnomad4 NFE

AF:

0.0660

Gnomad4 OTH

AF:

0.0397

Alfa

AF:

0.0566

Hom.:

112

Bravo

AF:

0.0375

Asia WGS

AF:

0.00924

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 31, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

3.9

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000082

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over