rs58559714

Positions:

chr21-46411395-G-A

Variant summary

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

The NM_006031.6(PCNT):c.5322G>A(p.Glu1774=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 1,613,660 control chromosomes in the GnomAD database, including 12,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 4501 hom., cov: 34)

Exomes 𝑓: 0.081 ( 7712 hom. )

Consequence

PCNT
NM_006031.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.524

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 21-46411395-G-A is Benign according to our data. Variant chr21-46411395-G-A is described in ClinVar as [Benign]. Clinvar id is 138619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46411395-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.524 with no splicing effect.

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	UniProt
PCNT	NM_006031.6 linkuse as main transcript	c.5322G>A	p.Glu1774=	synonymous_variant	28/47	ENST00000359568.10
PCNT	NM_001315529.2 linkuse as main transcript	c.4968G>A	p.Glu1656=	synonymous_variant	28/47

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNT	ENST00000359568.10 linkuse as main transcript	c.5322G>A	p.Glu1774=	synonymous_variant	28/47	1	NM_006031.6	P2	O95613-1
PCNT	ENST00000480896.5 linkuse as main transcript	c.4968G>A	p.Glu1656=	synonymous_variant	28/47	1		A2	O95613-2
PCNT	ENST00000695558.1 linkuse as main transcript	c.5355G>A	p.Glu1785=	synonymous_variant	29/48			A2
PCNT	ENST00000703224.1 linkuse as main transcript	c.*4565G>A		3_prime_UTR_variant, NMD_transcript_variant	30/49

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27100

AN:

152154

Hom.:

4496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.440

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0944

Gnomad ASJ

AF:

0.0861

Gnomad EAS

AF:

0.00578

Gnomad SAS

AF:

0.0919

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0755

Gnomad OTH

AF:

0.162

GnomAD3 exomes

AF:

0.0952

AC:

23738

AN:

249288

Hom.:

2198

AF XY:

0.0905

AC XY:

12234

AN XY:

135234

show subpopulations

Gnomad AFR exome

AF:

0.451

Gnomad AMR exome

AF:

0.0547

Gnomad ASJ exome

AF:

0.0865

Gnomad EAS exome

AF:

0.00317

Gnomad SAS exome

AF:

0.0879

Gnomad FIN exome

AF:

0.108

Gnomad NFE exome

AF:

0.0743

Gnomad OTH exome

AF:

0.0807

GnomAD4 exome

AF:

0.0814

AC:

118934

AN:

1461388

Hom.:

7712

Cov.:

AF XY:

0.0805

AC XY:

58514

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.461

Gnomad4 AMR exome

AF:

0.0592

Gnomad4 ASJ exome

AF:

0.0849

Gnomad4 EAS exome

AF:

0.00169

Gnomad4 SAS exome

AF:

0.0848

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.0715

Gnomad4 OTH exome

AF:

0.0970

GnomAD4 genome

AF:

0.178

AC:

27139

AN:

152272

Hom.:

4501

Cov.:

AF XY:

0.175

AC XY:

13037

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.439

Gnomad4 AMR

AF:

0.0941

Gnomad4 ASJ

AF:

0.0861

Gnomad4 EAS

AF:

0.00579

Gnomad4 SAS

AF:

0.0918

Gnomad4 FIN

AF:

0.107

Gnomad4 NFE

AF:

0.0755

Gnomad4 OTH

AF:

0.166

Alfa

AF:

0.125

Hom.:

1030

Bravo

AF:

0.188

Asia WGS

AF:

0.105

AC:

363

AN:

3478

EpiCase

AF:

0.0694

EpiControl

AF:

0.0699

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

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

-0.71

CADD

Benign

5.6

DANN

Benign

0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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