21-46413003-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006031.6(PCNT):c.6150+11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,414,308 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 14 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 11 hom. )

Failed GnomAD Quality Control

Consequence

PCNT
NM_006031.6 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.316

Publications

0 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 (BayesDel_noAF=-0.83).

BP6

Variant 21-46413003-G-C is Benign according to our data. Variant chr21-46413003-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 159629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.00103 (1455/1414308) while in subpopulation AFR AF = 0.0135 (428/31758). AF 95% confidence interval is 0.0124. There are 11 homozygotes in GnomAdExome4. There are 718 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNT	NM_006031.6 link	c.6150+11G>C		intron_variant	Intron 29 of 46	ENST00000359568.10	NP_006022.3	O95613-1
PCNT	NM_001315529.2 link	c.5796+11G>C		intron_variant	Intron 29 of 46		NP_001302458.1	O95613-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNT	ENST00000359568.10 link	c.6150+11G>C		intron_variant	Intron 29 of 46	1	NM_006031.6	ENSP00000352572.5		O95613-1

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1466

AN:

119418

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0318

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0112

Gnomad ASJ

AF:

0.00841

Gnomad EAS

AF:

0.00352

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00318

Gnomad MID

AF:

0.0144

Gnomad NFE

AF:

0.00349

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.00425

AC:

941

AN:

221224

AF XY:

0.00354

show subpopulations

Gnomad AFR exome

AF:

0.0288

Gnomad AMR exome

AF:

0.00542

Gnomad ASJ exome

AF:

0.00599

Gnomad EAS exome

AF:

0.000411

Gnomad FIN exome

AF:

0.000444

Gnomad NFE exome

AF:

0.00215

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00103

AC:

1455

AN:

1414308

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

718

AN XY:

703536

show subpopulations

African (AFR)

AF:

0.0135

AC:

428

AN:

31758

American (AMR)

AF:

0.00282

AC:

121

AN:

42940

Ashkenazi Jewish (ASJ)

AF:

0.00391

AC:

AN:

25318

East Asian (EAS)

AF:

0.000209

AC:

AN:

38254

South Asian (SAS)

AF:

0.000545

AC:

AN:

84470

European-Finnish (FIN)

AF:

0.000324

AC:

AN:

43186

Middle Eastern (MID)

AF:

0.00195

AC:

AN:

5630

European-Non Finnish (NFE)

AF:

0.000539

AC:

584

AN:

1084326

Other (OTH)

AF:

0.00246

AC:

144

AN:

58426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

136

203

271

339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0123

AC:

1471

AN:

119518

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

708

AN XY:

58376

show subpopulations

African (AFR)

AF:

0.0318

AC:

1053

AN:

33124

American (AMR)

AF:

0.0112

AC:

137

AN:

12226

Ashkenazi Jewish (ASJ)

AF:

0.00841

AC:

AN:

2736

East Asian (EAS)

AF:

0.00353

AC:

AN:

3680

South Asian (SAS)

AF:

0.00229

AC:

AN:

3498

European-Finnish (FIN)

AF:

0.00318

AC:

AN:

8170

Middle Eastern (MID)

AF:

0.0153

AC:

AN:

196

European-Non Finnish (NFE)

AF:

0.00349

AC:

187

AN:

53552

Other (OTH)

AF:

0.0125

AC:

AN:

1678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

110

165

220

275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00135

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Microcephalic osteodysplastic primordial dwarfism type II

Benign:2

Oct 23, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

not specified

Benign:1

Apr 25, 2013

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.1

(source)

DANN

Benign

0.32

PhyloP100

0.32

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over