rs61735824

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006031.6(PCNT):c.498A>G(p.Pro166Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0369 in 1,598,466 control chromosomes in the GnomAD database, including 1,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 120 hom., cov: 34)

Exomes 𝑓: 0.037 ( 1405 hom. )

Consequence

PCNT
NM_006031.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.46

Publications

4 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 21-46334627-A-G is Benign according to our data. Variant chr21-46334627-A-G is described in ClinVar as Benign. ClinVar VariationId is 138612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.46 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNT	NM_006031.6 link	c.498A>G	p.Pro166Pro	synonymous_variant	Exon 3 of 47	ENST00000359568.10	NP_006022.3	O95613-1
PCNT	NM_001315529.2 link	c.144A>G	p.Pro48Pro	synonymous_variant	Exon 3 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.498A>G	p.Pro166Pro	synonymous_variant	Exon 3 of 47	1	NM_006031.6	ENSP00000352572.5		O95613-1

Frequencies

GnomAD3 genomes

AF:

0.0348

AC:

5283

AN:

151692

Hom.:

122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0240

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.0363

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0178

Gnomad FIN

AF:

0.00547

Gnomad MID

AF:

0.0955

Gnomad NFE

AF:

0.0446

Gnomad OTH

AF:

0.0481

GnomAD2 exomes

AF:

0.0321

AC:

8006

AN:

249372

AF XY:

0.0329

show subpopulations

Gnomad AFR exome

AF:

0.0206

Gnomad AMR exome

AF:

0.0253

Gnomad ASJ exome

AF:

0.0986

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00716

Gnomad NFE exome

AF:

0.0439

Gnomad OTH exome

AF:

0.0426

GnomAD4 exome

AF:

0.0372

AC:

53750

AN:

1446656

Hom.:

1405

Cov.:

AF XY:

0.0372

AC XY:

26769

AN XY:

719826

show subpopulations

African (AFR)

AF:

0.0220

AC:

720

AN:

32770

American (AMR)

AF:

0.0265

AC:

1172

AN:

44210

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

2747

AN:

24916

East Asian (EAS)

AF:

0.000126

AC:

AN:

39666

South Asian (SAS)

AF:

0.0147

AC:

1254

AN:

85510

European-Finnish (FIN)

AF:

0.00825

AC:

439

AN:

53234

Middle Eastern (MID)

AF:

0.0787

AC:

449

AN:

5702

European-Non Finnish (NFE)

AF:

0.0405

AC:

44596

AN:

1101046

Other (OTH)

AF:

0.0397

AC:

2368

AN:

59602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.421

Heterozygous variant carriers

3447

6894

10340

13787

17234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1626

3252

4878

6504

8130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0348

AC:

5281

AN:

151810

Hom.:

120

Cov.:

AF XY:

0.0325

AC XY:

2412

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.0240

AC:

994

AN:

41456

American (AMR)

AF:

0.0363

AC:

553

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

386

AN:

3374

East Asian (EAS)

AF:

0.000193

AC:

AN:

5192

South Asian (SAS)

AF:

0.0180

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00547

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0856

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0446

AC:

3022

AN:

67812

Other (OTH)

AF:

0.0466

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

235

470

706

941

1176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0332

Hom.:

Bravo

AF:

0.0414

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 23, 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. -

Jul 30, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Microcephalic osteodysplastic primordial dwarfism type II

Benign:1

Jan 12, 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

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.2

(source)

DANN

Benign

0.12

PhyloP100

-1.5

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

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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