21-46411707-C-T

Position:

chr21-46411707-C-T

Variant summary

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

The NM_006031.6(PCNT):c.5634C>T(p.Asp1878=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0542 in 1,612,720 control chromosomes in the GnomAD database, including 2,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 224 hom., cov: 34)

Exomes 𝑓: 0.055 ( 2474 hom. )

Consequence

PCNT
NM_006031.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.18

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=-0.8).

BP6

Variant 21-46411707-C-T is Benign according to our data. Variant chr21-46411707-C-T is described in ClinVar as [Benign]. Clinvar id is 95338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46411707-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.18 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0614 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.5634C>T	p.Asp1878=	synonymous_variant	28/47	ENST00000359568.10
PCNT	NM_001315529.2 linkuse as main transcript	c.5280C>T	p.Asp1760=	synonymous_variant	28/47

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNT	ENST00000359568.10 linkuse as main transcript	c.5634C>T	p.Asp1878=	synonymous_variant	28/47	1	NM_006031.6	P2	O95613-1

Frequencies

GnomAD3 genomes

AF:

0.0486

AC:

7393

AN:

152218

Hom.:

225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0308

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0336

Gnomad ASJ

AF:

0.0709

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00869

Gnomad FIN

AF:

0.0841

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0630

Gnomad OTH

AF:

0.0492

GnomAD3 exomes

AF:

0.0457

AC:

11130

AN:

243466

Hom.:

288

AF XY:

0.0453

AC XY:

6039

AN XY:

133180

show subpopulations

Gnomad AFR exome

AF:

0.0312

Gnomad AMR exome

AF:

0.0216

Gnomad ASJ exome

AF:

0.0720

Gnomad EAS exome

AF:

0.000503

Gnomad SAS exome

AF:

0.0139

Gnomad FIN exome

AF:

0.0855

Gnomad NFE exome

AF:

0.0613

Gnomad OTH exome

AF:

0.0503

GnomAD4 exome

AF:

0.0548

AC:

80074

AN:

1460384

Hom.:

2474

Cov.:

AF XY:

0.0538

AC XY:

39060

AN XY:

726540

show subpopulations

Gnomad4 AFR exome

AF:

0.0284

Gnomad4 AMR exome

AF:

0.0234

Gnomad4 ASJ exome

AF:

0.0711

Gnomad4 EAS exome

AF:

0.000328

Gnomad4 SAS exome

AF:

0.0136

Gnomad4 FIN exome

AF:

0.0830

Gnomad4 NFE exome

AF:

0.0606

Gnomad4 OTH exome

AF:

0.0512

GnomAD4 genome

AF:

0.0486

AC:

7396

AN:

152336

Hom.:

224

Cov.:

AF XY:

0.0482

AC XY:

3589

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0308

Gnomad4 AMR

AF:

0.0335

Gnomad4 ASJ

AF:

0.0709

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00890

Gnomad4 FIN

AF:

0.0841

Gnomad4 NFE

AF:

0.0629

Gnomad4 OTH

AF:

0.0487

Alfa

AF:

0.0508

Hom.:

106

Bravo

AF:

0.0442

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0549

EpiControl

AF:

0.0545

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 07, 2013	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

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

-0.80

CADD

Benign

0.28

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

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