Variant rs140307278 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_006031.6(PCNT):c.6922-5_6922-4insTCTGA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0853 in 1,538,784 control chromosomes in the GnomAD database, including 10,658 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 4328 hom., cov: 30)

Exomes 𝑓: 0.075 ( 6330 hom. )

Consequence

PCNT
NM_006031.6 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.703

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 -16 ACMG points.

BP6

Variant 21-46418198-T-TATCTG is Benign according to our data. Variant chr21-46418198-T-TATCTG is described in ClinVar as [Benign]. Clinvar id is 159645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCNT	NM_006031.6 link	c.6922-5_6922-4insTCTGA		splice_region_variant, intron_variant		ENST00000359568.10	NP_006022.3	O95613-1
PCNT	NM_001315529.2 link	c.6568-5_6568-4insTCTGA		splice_region_variant, intron_variant			NP_001302458.1	O95613-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCNT	ENST00000359568.10 link	c.6922-6_6922-5insATCTG		splice_region_variant, intron_variant		1	NM_006031.6	ENSP00000352572.5		O95613-1

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26747

AN:

151932

Hom.:

4323

Cov.:

show subpopulations

Gnomad AFR

AF:

0.433

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0940

Gnomad ASJ

AF:

0.0862

Gnomad EAS

AF:

0.00558

Gnomad SAS

AF:

0.0920

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0762

Gnomad OTH

AF:

0.162

GnomAD3 exomes

AF:

0.0910

AC:

22642

AN:

248744

Hom.:

1996

AF XY:

0.0862

AC XY:

11609

AN XY:

134618

show subpopulations

Gnomad AFR exome

AF:

0.432

Gnomad AMR exome

AF:

0.0530

Gnomad ASJ exome

AF:

0.0825

Gnomad EAS exome

AF:

0.00315

Gnomad SAS exome

AF:

0.0844

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.0707

Gnomad OTH exome

AF:

0.0771

GnomAD4 exome

AF:

0.0754

AC:

104535

AN:

1386734

Hom.:

6330

Cov.:

AF XY:

0.0754

AC XY:

52372

AN XY:

694712

show subpopulations

Gnomad4 AFR exome

AF:

0.434

Gnomad4 AMR exome

AF:

0.0583

Gnomad4 ASJ exome

AF:

0.0814

Gnomad4 EAS exome

AF:

0.00160

Gnomad4 SAS exome

AF:

0.0821

Gnomad4 FIN exome

AF:

0.103

Gnomad4 NFE exome

AF:

0.0656

Gnomad4 OTH exome

AF:

0.0917

GnomAD4 genome

AF:

0.176

AC:

26785

AN:

152050

Hom.:

4328

Cov.:

AF XY:

0.173

AC XY:

12856

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.432

Gnomad4 AMR

AF:

0.0937

Gnomad4 ASJ

AF:

0.0862

Gnomad4 EAS

AF:

0.00559

Gnomad4 SAS

AF:

0.0919

Gnomad4 FIN

AF:

0.106

Gnomad4 NFE

AF:

0.0762

Gnomad4 OTH

AF:

0.166

Alfa

AF:

0.0692

Hom.:

139

Asia WGS

AF:

0.104

AC:

361

AN:

3478

EpiCase

AF:

0.0695

EpiControl

AF:

0.0678

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Microcephalic osteodysplastic primordial dwarfism type II

Benign:2

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	May 31, 2017	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 10, 2014

- -

Microcephalic osteodysplastic primordial dwarfism

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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