rs34268261

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006031.6(PCNT):c.5858G>A(p.Arg1953His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0541 in 1,592,096 control chromosomes in the GnomAD database, including 2,654 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1953S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.049 ( 227 hom., cov: 33)

Exomes 𝑓: 0.055 ( 2427 hom. )

Consequence

PCNT
NM_006031.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.42

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

microcephalic osteodysplastic primordial dwarfism type II
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
Moyamoya disease
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp

PCNT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018873513).

BP6

Variant 21-46411931-G-A is Benign according to our data. Variant chr21-46411931-G-A is described in ClinVar as [Benign]. Clinvar id is 95340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
PCNT	NM_006031.6 link	c.5858G>A	p.Arg1953His	missense_variant	Exon 28 of 47	ENST00000359568.10	NP_006022.3	O95613-1
PCNT	NM_001315529.2 link	c.5504G>A	p.Arg1835His	missense_variant	Exon 28 of 47		NP_001302458.1	O95613-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNT	ENST00000359568.10 link	c.5858G>A	p.Arg1953His	missense_variant	Exon 28 of 47	1	NM_006031.6	ENSP00000352572.5		O95613-1

Frequencies

GnomAD3 genomes

AF:

0.0486

AC:

7394

AN:

152164

Hom.:

228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0307

Gnomad AMI

AF:

0.0275

Gnomad AMR

AF:

0.0337

Gnomad ASJ

AF:

0.0710

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00869

Gnomad FIN

AF:

0.0841

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0630

Gnomad OTH

AF:

0.0493

GnomAD2 exomes

AF:

0.0442

AC:

9426

AN:

213106

AF XY:

0.0438

show subpopulations

Gnomad AFR exome

AF:

0.0304

Gnomad AMR exome

AF:

0.0217

Gnomad ASJ exome

AF:

0.0736

Gnomad EAS exome

AF:

0.0000598

Gnomad FIN exome

AF:

0.0887

Gnomad NFE exome

AF:

0.0625

Gnomad OTH exome

AF:

0.0511

GnomAD4 exome

AF:

0.0547

AC:

78714

AN:

1439814

Hom.:

2427

Cov.:

AF XY:

0.0536

AC XY:

38378

AN XY:

716330

show subpopulations

African (AFR)

AF:

0.0285

AC:

949

AN:

33306

American (AMR)

AF:

0.0236

AC:

1034

AN:

43906

Ashkenazi Jewish (ASJ)

AF:

0.0712

AC:

1846

AN:

25944

East Asian (EAS)

AF:

0.000127

AC:

AN:

39336

South Asian (SAS)

AF:

0.0138

AC:

1180

AN:

85320

European-Finnish (FIN)

AF:

0.0832

AC:

3216

AN:

38638

Middle Eastern (MID)

AF:

0.0316

AC:

148

AN:

4682

European-Non Finnish (NFE)

AF:

0.0607

AC:

67291

AN:

1108898

Other (OTH)

AF:

0.0509

AC:

3045

AN:

59784

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

4985

9970

14954

19939

24924

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0486

AC:

7397

AN:

152282

Hom.:

227

Cov.:

AF XY:

0.0482

AC XY:

3590

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0308

AC:

1279

AN:

41570

American (AMR)

AF:

0.0336

AC:

514

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0710

AC:

246

AN:

3466

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.00891

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0841

AC:

893

AN:

10614

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0630

AC:

4283

AN:

68002

Other (OTH)

AF:

0.0488

AC:

103

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

360

720

1081

1441

1801

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0579

Hom.:

Bravo

AF:

0.0441

TwinsUK

AF:

0.0550

AC:

204

ALSPAC

AF:

0.0586

AC:

226

ESP6500AA

AF:

0.0331

AC:

143

ESP6500EA

AF:

0.0576

AC:

487

ExAC

AF:

0.0432

AC:

5136

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 07, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 31, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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:3

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Microcephalic osteodysplastic primordial dwarfism type II

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.0050

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.015

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0053

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.55

PhyloP100

-2.4

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.77

REVEL

Benign

0.031

Sift

Benign

0.27

Sift4G

Benign

0.17

Polyphen

0.0010

Vest4

0.015

MPC

0.10

ClinPred

0.0081

GERP RS

-11

Varity_R

0.023

gMVP

0.068

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs34268261

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over