rs61735805

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006031.6(PCNT):c.3339T>C(p.Ser1113=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 1,614,146 control chromosomes in the GnomAD database, including 1,665 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 100 hom., cov: 33)

Exomes 𝑓: 0.043 ( 1565 hom. )

Consequence

PCNT
NM_006031.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.537

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=-0.9).

BP6

Variant 21-46385858-T-C is Benign according to our data. Variant chr21-46385858-T-C is described in ClinVar as [Benign]. Clinvar id is 159585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46385858-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.537 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0306 (4659/152312) while in subpopulation NFE AF= 0.0486 (3305/68022). AF 95% confidence interval is 0.0472. There are 100 homozygotes in gnomad4. There are 2189 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 100 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCNT	NM_006031.6 linkuse as main transcript	c.3339T>C	p.Ser1113=	synonymous_variant	17/47	ENST00000359568.10
PCNT	NM_001315529.2 linkuse as main transcript	c.2985T>C	p.Ser995=	synonymous_variant	17/47

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNT	ENST00000359568.10 linkuse as main transcript	c.3339T>C	p.Ser1113=	synonymous_variant	17/47	1	NM_006031.6	P2	O95613-1

Frequencies

GnomAD3 genomes

AF:

0.0306

AC:

4660

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00770

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0191

Gnomad ASJ

AF:

0.0458

Gnomad EAS

AF:

0.000961

Gnomad SAS

AF:

0.0251

Gnomad FIN

AF:

0.0333

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0486

Gnomad OTH

AF:

0.0258

GnomAD3 exomes

AF:

0.0355

AC:

8923

AN:

251494

Hom.:

208

AF XY:

0.0368

AC XY:

4996

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00757

Gnomad AMR exome

AF:

0.0198

Gnomad ASJ exome

AF:

0.0467

Gnomad EAS exome

AF:

0.00125

Gnomad SAS exome

AF:

0.0320

Gnomad FIN exome

AF:

0.0388

Gnomad NFE exome

AF:

0.0492

Gnomad OTH exome

AF:

0.0337

GnomAD4 exome

AF:

0.0432

AC:

63162

AN:

1461834

Hom.:

1565

Cov.:

AF XY:

0.0433

AC XY:

31484

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00621

Gnomad4 AMR exome

AF:

0.0205

Gnomad4 ASJ exome

AF:

0.0443

Gnomad4 EAS exome

AF:

0.000781

Gnomad4 SAS exome

AF:

0.0342

Gnomad4 FIN exome

AF:

0.0401

Gnomad4 NFE exome

AF:

0.0478

Gnomad4 OTH exome

AF:

0.0399

GnomAD4 genome

AF:

0.0306

AC:

4659

AN:

152312

Hom.:

100

Cov.:

AF XY:

0.0294

AC XY:

2189

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00767

Gnomad4 AMR

AF:

0.0190

Gnomad4 ASJ

AF:

0.0458

Gnomad4 EAS

AF:

0.000963

Gnomad4 SAS

AF:

0.0253

Gnomad4 FIN

AF:

0.0333

Gnomad4 NFE

AF:

0.0486

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.0441

Hom.:

Bravo

AF:

0.0282

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0467

EpiControl

AF:

0.0424

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Microcephalic osteodysplastic primordial dwarfism type II

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Jun 28, 2017	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 08, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.67

DANN

Benign

0.40

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