rs61407822

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_006031.6(PCNT):c.2415C>G(p.Ala805Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 1,614,106 control chromosomes in the GnomAD database, including 7,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 3523 hom., cov: 33)

Exomes 𝑓: 0.026 ( 3645 hom. )

Consequence

PCNT
NM_006031.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.146

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=-0.66).

BP6

Variant 21-46363740-C-G is Benign according to our data. Variant chr21-46363740-C-G is described in ClinVar as [Benign]. Clinvar id is 138616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46363740-C-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.146 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNT	NM_006031.6 link	c.2415C>G	p.Ala805Ala	synonymous_variant	Exon 14 of 47	ENST00000359568.10	NP_006022.3	O95613-1
PCNT	NM_001315529.2 link	c.2061C>G	p.Ala687Ala	synonymous_variant	Exon 14 of 47		NP_001302458.1	O95613-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNT	ENST00000359568.10 link	c.2415C>G	p.Ala805Ala	synonymous_variant	Exon 14 of 47	1	NM_006031.6	ENSP00000352572.5		O95613-1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19579

AN:

152118

Hom.:

3520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.406

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0606

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.00559

Gnomad SAS

AF:

0.0828

Gnomad FIN

AF:

0.0225

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.111

GnomAD3 exomes

AF:

0.0498

AC:

12511

AN:

251384

Hom.:

1536

AF XY:

0.0450

AC XY:

6116

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.416

Gnomad AMR exome

AF:

0.0331

Gnomad ASJ exome

AF:

0.0151

Gnomad EAS exome

AF:

0.00364

Gnomad SAS exome

AF:

0.0738

Gnomad FIN exome

AF:

0.0220

Gnomad NFE exome

AF:

0.0128

Gnomad OTH exome

AF:

0.0310

GnomAD4 exome

AF:

0.0265

AC:

38739

AN:

1461870

Hom.:

3645

Cov.:

AF XY:

0.0267

AC XY:

19434

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.428

Gnomad4 AMR exome

AF:

0.0358

Gnomad4 ASJ exome

AF:

0.0147

Gnomad4 EAS exome

AF:

0.00194

Gnomad4 SAS exome

AF:

0.0708

Gnomad4 FIN exome

AF:

0.0203

Gnomad4 NFE exome

AF:

0.0109

Gnomad4 OTH exome

AF:

0.0453

GnomAD4 genome

AF:

0.129

AC:

19619

AN:

152236

Hom.:

3523

Cov.:

AF XY:

0.126

AC XY:

9384

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.406

Gnomad4 AMR

AF:

0.0605

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.00560

Gnomad4 SAS

AF:

0.0825

Gnomad4 FIN

AF:

0.0225

Gnomad4 NFE

AF:

0.0126

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.0215

Hom.:

Bravo

AF:

0.143

Asia WGS

AF:

0.0920

AC:

318

AN:

3478

EpiCase

AF:

0.0146

EpiControl

AF:

0.0156

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 26, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Microcephalic osteodysplastic primordial dwarfism type II

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-0.66

CADD

Benign

6.4

DANN

Benign

0.50

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