Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006031.6(PCNT):c.3339T>C(p.Ser1113Ser) 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

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=-0.9).

BP6

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

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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 100 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006031.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNT	NM_006031.6	MANE Select	c.3339T>C	p.Ser1113Ser	synonymous	Exon 17 of 47	NP_006022.3
	PCNT	NM_001315529.2		c.2985T>C	p.Ser995Ser	synonymous	Exon 17 of 47	NP_001302458.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PCNT	ENST00000359568.10	TSL:1 MANE Select	c.3339T>C	p.Ser1113Ser	synonymous	Exon 17 of 47	ENSP00000352572.5
PCNT	ENST00000480896.5	TSL:1	c.2985T>C	p.Ser995Ser	synonymous	Exon 17 of 47	ENSP00000511989.1
PCNT	ENST00000695558.1		c.3339T>C	p.Ser1113Ser	synonymous	Exon 17 of 48	ENSP00000512015.1

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

GnomAD2 exomes

AF:

0.0355

AC:

8923

AN:

251494

AF XY:

0.0368

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 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

African (AFR)

AF:

0.00621

AC:

208

AN:

33480

American (AMR)

AF:

0.0205

AC:

915

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0443

AC:

1157

AN:

26136

East Asian (EAS)

AF:

0.000781

AC:

AN:

39700

South Asian (SAS)

AF:

0.0342

AC:

2949

AN:

86258

European-Finnish (FIN)

AF:

0.0401

AC:

2144

AN:

53418

Middle Eastern (MID)

AF:

0.0368

AC:

212

AN:

5768

European-Non Finnish (NFE)

AF:

0.0478

AC:

53139

AN:

1111954

Other (OTH)

AF:

0.0399

AC:

2407

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

3409

6819

10228

13638

17047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1920

3840

5760

7680

9600

<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:

0.0306

AC:

4659

AN:

152312

Hom.:

100

Cov.:

AF XY:

0.0294

AC XY:

2189

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00767

AC:

319

AN:

41570

American (AMR)

AF:

0.0190

AC:

291

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0458

AC:

159

AN:

3470

East Asian (EAS)

AF:

0.000963

AC:

AN:

5190

South Asian (SAS)

AF:

0.0253

AC:

122

AN:

4822

European-Finnish (FIN)

AF:

0.0333

AC:

353

AN:

10614

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0486

AC:

3305

AN:

68022

Other (OTH)

AF:

0.0255

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

228

455

683

910

1138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0386

Hom.:

124

Bravo

AF:

0.0282

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0467

EpiControl

AF:

0.0424

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Microcephalic osteodysplastic primordial dwarfism type II (3)

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.67

(source)

DANN

Benign

0.40

PhyloP100

-0.54

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over