rs61735824

Positions:

chr21-46334627-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006031.6(PCNT):c.498A>G(p.Pro166Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0369 in 1,598,466 control chromosomes in the GnomAD database, including 1,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 120 hom., cov: 34)

Exomes 𝑓: 0.037 ( 1405 hom. )

Consequence

PCNT
NM_006031.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.46

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:

PCNT (HGNC:):

PCNT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 21-46334627-A-G is Benign according to our data. Variant chr21-46334627-A-G is described in ClinVar as [Benign]. Clinvar id is 138612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46334627-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.46 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0727 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.498A>G	p.Pro166Pro	synonymous_variant	3/47	ENST00000359568.10	NP_006022.3	O95613-1
PCNT	NM_001315529.2 linkuse as main transcript	c.144A>G	p.Pro48Pro	synonymous_variant	3/47		NP_001302458.1	O95613-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCNT	ENST00000359568.10 linkuse as main transcript	c.498A>G	p.Pro166Pro	synonymous_variant	3/47	1	NM_006031.6	ENSP00000352572.5		O95613-1

Frequencies

GnomAD3 genomes

AF:

0.0348

AC:

5283

AN:

151692

Hom.:

122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0240

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.0363

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0178

Gnomad FIN

AF:

0.00547

Gnomad MID

AF:

0.0955

Gnomad NFE

AF:

0.0446

Gnomad OTH

AF:

0.0481

GnomAD3 exomes

AF:

0.0321

AC:

8006

AN:

249372

Hom.:

226

AF XY:

0.0329

AC XY:

4439

AN XY:

134900

show subpopulations

Gnomad AFR exome

AF:

0.0206

Gnomad AMR exome

AF:

0.0253

Gnomad ASJ exome

AF:

0.0986

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0156

Gnomad FIN exome

AF:

0.00716

Gnomad NFE exome

AF:

0.0439

Gnomad OTH exome

AF:

0.0426

GnomAD4 exome

AF:

0.0372

AC:

53750

AN:

1446656

Hom.:

1405

Cov.:

AF XY:

0.0372

AC XY:

26769

AN XY:

719826

show subpopulations

Gnomad4 AFR exome

AF:

0.0220

Gnomad4 AMR exome

AF:

0.0265

Gnomad4 ASJ exome

AF:

0.110

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0147

Gnomad4 FIN exome

AF:

0.00825

Gnomad4 NFE exome

AF:

0.0405

Gnomad4 OTH exome

AF:

0.0397

GnomAD4 genome

AF:

0.0348

AC:

5281

AN:

151810

Hom.:

120

Cov.:

AF XY:

0.0325

AC XY:

2412

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.0240

Gnomad4 AMR

AF:

0.0363

Gnomad4 ASJ

AF:

0.114

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0180

Gnomad4 FIN

AF:

0.00547

Gnomad4 NFE

AF:

0.0446

Gnomad4 OTH

AF:

0.0466

Alfa

AF:

0.0332

Hom.:

Bravo

AF:

0.0414

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 30, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 23, 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Microcephalic osteodysplastic primordial dwarfism type II

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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

-0.98

CADD

Benign

1.2

DANN

Benign

0.12

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