chr21-46430241-G-C

Position:

chr21-46430241-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000359568.10(PCNT):c.7913+9G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0908 in 1,608,684 control chromosomes in the GnomAD database, including 12,242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 4500 hom., cov: 33)

Exomes 𝑓: 0.082 ( 7742 hom. )

Consequence

PCNT
ENST00000359568.10 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.337

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 21-46430241-G-C is Benign according to our data. Variant chr21-46430241-G-C is described in ClinVar as [Benign]. Clinvar id is 138608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46430241-G-C is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
PCNT	NM_006031.6 linkuse as main transcript	c.7913+9G>C		intron_variant		ENST00000359568.10	NP_006022.3
PCNT	NM_001315529.2 linkuse as main transcript	c.7559+9G>C		intron_variant			NP_001302458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCNT	ENST00000359568.10 linkuse as main transcript	c.7913+9G>C		intron_variant		1	NM_006031.6	ENSP00000352572	P2	O95613-1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27095

AN:

152058

Hom.:

4494

Cov.:

show subpopulations

Gnomad AFR

AF:

0.440

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0942

Gnomad ASJ

AF:

0.0865

Gnomad EAS

AF:

0.00559

Gnomad SAS

AF:

0.0902

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0762

Gnomad OTH

AF:

0.164

GnomAD3 exomes

AF:

0.0958

AC:

23762

AN:

247964

Hom.:

2185

AF XY:

0.0904

AC XY:

12148

AN XY:

134362

show subpopulations

Gnomad AFR exome

AF:

0.450

Gnomad AMR exome

AF:

0.0548

Gnomad ASJ exome

AF:

0.0865

Gnomad EAS exome

AF:

0.00311

Gnomad SAS exome

AF:

0.0876

Gnomad FIN exome

AF:

0.109

Gnomad NFE exome

AF:

0.0747

Gnomad OTH exome

AF:

0.0827

GnomAD4 exome

AF:

0.0816

AC:

118900

AN:

1456508

Hom.:

7742

Cov.:

AF XY:

0.0807

AC XY:

58502

AN XY:

724686

show subpopulations

Gnomad4 AFR exome

AF:

0.462

Gnomad4 AMR exome

AF:

0.0593

Gnomad4 ASJ exome

AF:

0.0849

Gnomad4 EAS exome

AF:

0.00169

Gnomad4 SAS exome

AF:

0.0841

Gnomad4 FIN exome

AF:

0.103

Gnomad4 NFE exome

AF:

0.0719

Gnomad4 OTH exome

AF:

0.0972

GnomAD4 genome

AF:

0.178

AC:

27135

AN:

152176

Hom.:

4500

Cov.:

AF XY:

0.175

AC XY:

13005

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.439

Gnomad4 AMR

AF:

0.0940

Gnomad4 ASJ

AF:

0.0865

Gnomad4 EAS

AF:

0.00560

Gnomad4 SAS

AF:

0.0900

Gnomad4 FIN

AF:

0.107

Gnomad4 NFE

AF:

0.0761

Gnomad4 OTH

AF:

0.167

Alfa

AF:

0.0745

Hom.:

232

Bravo

AF:

0.189

Asia WGS

AF:

0.104

AC:

362

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 26, 2014	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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Microcephalic osteodysplastic primordial dwarfism type II

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

-0.88

CADD

Benign

2.4

DANN

Benign

0.35

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

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