chr21-46413003-G-C

Position:

chr21-46413003-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).

BP6

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

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome 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 gnomad4_exome. There are 718 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCNT	NM_006031.6 linkuse as main transcript	c.6150+11G>C		intron_variant		ENST00000359568.10
PCNT	NM_001315529.2 linkuse as main transcript	c.5796+11G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNT	ENST00000359568.10 linkuse as main transcript	c.6150+11G>C		intron_variant		1	NM_006031.6	P2	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

GnomAD3 exomes

AF:

0.00425

AC:

941

AN:

221224

Hom.:

AF XY:

0.00354

AC XY:

426

AN XY:

120238

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 SAS exome

AF:

0.00127

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

Gnomad4 AFR exome

AF:

0.0135

Gnomad4 AMR exome

AF:

0.00282

Gnomad4 ASJ exome

AF:

0.00391

Gnomad4 EAS exome

AF:

0.000209

Gnomad4 SAS exome

AF:

0.000545

Gnomad4 FIN exome

AF:

0.000324

Gnomad4 NFE exome

AF:

0.000539

Gnomad4 OTH exome

AF:

0.00246

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

Gnomad4 AFR

AF:

0.0318

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.00841

Gnomad4 EAS

AF:

0.00353

Gnomad4 SAS

AF:

0.00229

Gnomad4 FIN

AF:

0.00318

Gnomad4 NFE

AF:

0.00349

Gnomad4 OTH

AF:

0.0125

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

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
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	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Apr 02, 2020	- -
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. -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 25, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.1

DANN

Benign

0.32

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

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

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