21-46334557-GTGGGATGTTCACAGTCAGTGACCACCCACCAGAACAGCA-GTGGGATGTTCACAGTCAGTGACCACCCACCAGAACAGCATGGGATGTTCACAGTCAGTGACCACCCACCAGAACAGCA

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1

The NM_006031.6(PCNT):c.467_505dupATGGGATGTTCACAGTCAGTGACCACCCACCAGAACAGC(p.His156_Gln168dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 140,682 control chromosomes in the GnomAD database, including 215 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 215 hom., cov: 33)

Exomes 𝑓: 0.014 ( 1406 hom. )

Failed GnomAD Quality Control

Consequence

PCNT
NM_006031.6 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.13

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_006031.6.

BP6

Variant 21-46334557-G-GTGGGATGTTCACAGTCAGTGACCACCCACCAGAACAGCA is Benign according to our data. Variant chr21-46334557-G-GTGGGATGTTCACAGTCAGTGACCACCCACCAGAACAGCA is described in ClinVar as [Likely_benign]. Clinvar id is 211862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNT	NM_006031.6 link	c.467_505dupATGGGATGTTCACAGTCAGTGACCACCCACCAGAACAGC	p.His156_Gln168dup	disruptive_inframe_insertion	Exon 3 of 47	ENST00000359568.10	NP_006022.3	O95613-1
PCNT	NM_001315529.2 link	c.113_151dupATGGGATGTTCACAGTCAGTGACCACCCACCAGAACAGC	p.His38_Gln50dup	disruptive_inframe_insertion	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.467_505dupATGGGATGTTCACAGTCAGTGACCACCCACCAGAACAGC	p.His156_Gln168dup	disruptive_inframe_insertion	Exon 3 of 47	1	NM_006031.6	ENSP00000352572.5		O95613-1

Frequencies

GnomAD3 genomes

AF:

0.0463

AC:

6515

AN:

140566

Hom.:

215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0606

Gnomad AMI

AF:

0.0366

Gnomad AMR

AF:

0.0367

Gnomad ASJ

AF:

0.0521

Gnomad EAS

AF:

0.00526

Gnomad SAS

AF:

0.0172

Gnomad FIN

AF:

0.0335

Gnomad MID

AF:

0.0464

Gnomad NFE

AF:

0.0475

Gnomad OTH

AF:

0.0456

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0144

AC:

19791

AN:

1376124

Hom.:

1406

Cov.:

AF XY:

0.0146

AC XY:

9986

AN XY:

684758

show subpopulations

Gnomad4 AFR exome

AF:

0.0301

Gnomad4 AMR exome

AF:

0.0103

Gnomad4 ASJ exome

AF:

0.0349

Gnomad4 EAS exome

AF:

0.00668

Gnomad4 SAS exome

AF:

0.00509

Gnomad4 FIN exome

AF:

0.0384

Gnomad4 NFE exome

AF:

0.0131

Gnomad4 OTH exome

AF:

0.0214

GnomAD4 genome

AF:

0.0463

AC:

6519

AN:

140682

Hom.:

215

Cov.:

AF XY:

0.0437

AC XY:

3004

AN XY:

68752

show subpopulations

Gnomad4 AFR

AF:

0.0606

Gnomad4 AMR

AF:

0.0366

Gnomad4 ASJ

AF:

0.0521

Gnomad4 EAS

AF:

0.00527

Gnomad4 SAS

AF:

0.0170

Gnomad4 FIN

AF:

0.0335

Gnomad4 NFE

AF:

0.0475

Gnomad4 OTH

AF:

0.0451

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Nov 29, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

- -

Jul 31, 2018

GeneDx

Significance: Benign

Review Status: flagged submission

Collection Method: clinical testing

- -

Microcephalic osteodysplastic primordial dwarfism type II

Benign:2

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 22, 2017

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Jul 31, 2015

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PCNT-related disorder

Benign:1

Sep 28, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over