21-46411395-G-A

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.5322G>A(p.Glu1774Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 1,613,660 control chromosomes in the GnomAD database, including 12,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 4501 hom., cov: 34)

Exomes 𝑓: 0.081 ( 7712 hom. )

Consequence

PCNT
NM_006031.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.524

Publications

8 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=-0.71).

BP6

Variant 21-46411395-G-A is Benign according to our data. Variant chr21-46411395-G-A is described in CliVar as Benign. Clinvar id is 138619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46411395-G-A is described in CliVar as Benign. Clinvar id is 138619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46411395-G-A is described in CliVar as Benign. Clinvar id is 138619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46411395-G-A is described in CliVar as Benign. Clinvar id is 138619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46411395-G-A is described in CliVar as Benign. Clinvar id is 138619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.524 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNT	NM_006031.6 link	c.5322G>A	p.Glu1774Glu	synonymous_variant	Exon 28 of 47	ENST00000359568.10	NP_006022.3	O95613-1
PCNT	NM_001315529.2 link	c.4968G>A	p.Glu1656Glu	synonymous_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.5322G>A	p.Glu1774Glu	synonymous_variant	Exon 28 of 47	1	NM_006031.6	ENSP00000352572.5		O95613-1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27100

AN:

152154

Hom.:

4496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.440

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0944

Gnomad ASJ

AF:

0.0861

Gnomad EAS

AF:

0.00578

Gnomad SAS

AF:

0.0919

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0755

Gnomad OTH

AF:

0.162

GnomAD2 exomes

AF:

0.0952

AC:

23738

AN:

249288

AF XY:

0.0905

show subpopulations

Gnomad AFR exome

AF:

0.451

Gnomad AMR exome

AF:

0.0547

Gnomad ASJ exome

AF:

0.0865

Gnomad EAS exome

AF:

0.00317

Gnomad FIN exome

AF:

0.108

Gnomad NFE exome

AF:

0.0743

Gnomad OTH exome

AF:

0.0807

GnomAD4 exome

AF:

0.0814

AC:

118934

AN:

1461388

Hom.:

7712

Cov.:

AF XY:

0.0805

AC XY:

58514

AN XY:

727006

show subpopulations

African (AFR)

AF:

0.461

AC:

15429

AN:

33478

American (AMR)

AF:

0.0592

AC:

2647

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0849

AC:

2218

AN:

26136

East Asian (EAS)

AF:

0.00169

AC:

AN:

39700

South Asian (SAS)

AF:

0.0848

AC:

7317

AN:

86256

European-Finnish (FIN)

AF:

0.104

AC:

5485

AN:

52968

Middle Eastern (MID)

AF:

0.0735

AC:

424

AN:

5766

European-Non Finnish (NFE)

AF:

0.0715

AC:

79492

AN:

1111972

Other (OTH)

AF:

0.0970

AC:

5855

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

6774

13547

20321

27094

33868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3082

6164

9246

12328

15410

<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:

0.178

AC:

27139

AN:

152272

Hom.:

4501

Cov.:

AF XY:

0.175

AC XY:

13037

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.439

AC:

18252

AN:

41540

American (AMR)

AF:

0.0941

AC:

1441

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0861

AC:

299

AN:

3472

East Asian (EAS)

AF:

0.00579

AC:

AN:

5178

South Asian (SAS)

AF:

0.0918

AC:

443

AN:

4826

European-Finnish (FIN)

AF:

0.107

AC:

1136

AN:

10618

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0755

AC:

5134

AN:

68010

Other (OTH)

AF:

0.166

AC:

351

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

980

1960

2939

3919

4899

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

246

492

738

984

1230

<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:

0.125

Hom.:

1030

Bravo

AF:

0.188

Asia WGS

AF:

0.105

AC:

363

AN:

3478

EpiCase

AF:

0.0694

EpiControl

AF:

0.0699

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 26, 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: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 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

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.6

(source)

DANN

Benign

0.35

PhyloP100

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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