chr21-46428436-G-A

Position:

chr21-46428436-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006031.6(PCNT):c.7536G>A(p.Pro2512=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0545 in 1,612,398 control chromosomes in the GnomAD database, including 2,747 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 226 hom., cov: 33)

Exomes 𝑓: 0.055 ( 2521 hom. )

Consequence

PCNT
NM_006031.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.59

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 21-46428436-G-A is Benign according to our data. Variant chr21-46428436-G-A is described in ClinVar as [Benign]. Clinvar id is 138603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46428436-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.59 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCNT	NM_006031.6 linkuse as main transcript	c.7536G>A	p.Pro2512=	synonymous_variant	35/47	ENST00000359568.10
PCNT	NM_001315529.2 linkuse as main transcript	c.7182G>A	p.Pro2394=	synonymous_variant	35/47

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNT	ENST00000359568.10 linkuse as main transcript	c.7536G>A	p.Pro2512=	synonymous_variant	35/47	1	NM_006031.6	P2	O95613-1

Frequencies

GnomAD3 genomes

AF:

0.0475

AC:

7234

AN:

152240

Hom.:

227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0252

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0335

Gnomad ASJ

AF:

0.0712

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00889

Gnomad FIN

AF:

0.0850

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0638

Gnomad OTH

AF:

0.0493

GnomAD3 exomes

AF:

0.0459

AC:

11394

AN:

248050

Hom.:

310

AF XY:

0.0455

AC XY:

6136

AN XY:

134900

show subpopulations

Gnomad AFR exome

AF:

0.0251

Gnomad AMR exome

AF:

0.0220

Gnomad ASJ exome

AF:

0.0718

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0141

Gnomad FIN exome

AF:

0.0867

Gnomad NFE exome

AF:

0.0620

Gnomad OTH exome

AF:

0.0516

GnomAD4 exome

AF:

0.0552

AC:

80630

AN:

1460040

Hom.:

2521

Cov.:

AF XY:

0.0542

AC XY:

39372

AN XY:

726302

show subpopulations

Gnomad4 AFR exome

AF:

0.0227

Gnomad4 AMR exome

AF:

0.0239

Gnomad4 ASJ exome

AF:

0.0711

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0139

Gnomad4 FIN exome

AF:

0.0835

Gnomad4 NFE exome

AF:

0.0613

Gnomad4 OTH exome

AF:

0.0513

GnomAD4 genome

AF:

0.0475

AC:

7232

AN:

152358

Hom.:

226

Cov.:

AF XY:

0.0470

AC XY:

3502

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0252

Gnomad4 AMR

AF:

0.0334

Gnomad4 ASJ

AF:

0.0712

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00911

Gnomad4 FIN

AF:

0.0850

Gnomad4 NFE

AF:

0.0638

Gnomad4 OTH

AF:

0.0488

Alfa

AF:

0.0498

Hom.:

116

Bravo

AF:

0.0429

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0558

EpiControl

AF:

0.0555

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	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. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

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

-0.88

CADD

Benign

0.058

DANN

Benign

0.41

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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