21-46416836-T-C

Position:

chr21-46416836-T-C

Variant summary

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

The NM_006031.6(PCNT):c.6918T>C(p.Ala2306=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0411 in 1,597,378 control chromosomes in the GnomAD database, including 1,766 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 150 hom., cov: 33)

Exomes 𝑓: 0.042 ( 1616 hom. )

Consequence

PCNT
NM_006031.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0220

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=-0.83).

BP6

Variant 21-46416836-T-C is Benign according to our data. Variant chr21-46416836-T-C is described in ClinVar as [Benign]. Clinvar id is 159643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46416836-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.022 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0779 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.6918T>C	p.Ala2306=	synonymous_variant	30/47	ENST00000359568.10	NP_006022.3
PCNT	NM_001315529.2 linkuse as main transcript	c.6564T>C	p.Ala2188=	synonymous_variant	30/47		NP_001302458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCNT	ENST00000359568.10 linkuse as main transcript	c.6918T>C	p.Ala2306=	synonymous_variant	30/47	1	NM_006031.6	ENSP00000352572	P2	O95613-1

Frequencies

GnomAD3 genomes

AF:

0.0351

AC:

5337

AN:

152176

Hom.:

151

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0204

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.0374

Gnomad ASJ

AF:

0.145

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0180

Gnomad FIN

AF:

0.00537

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0452

Gnomad OTH

AF:

0.0501

GnomAD3 exomes

AF:

0.0379

AC:

8655

AN:

228324

Hom.:

280

AF XY:

0.0381

AC XY:

4817

AN XY:

126276

show subpopulations

Gnomad AFR exome

AF:

0.0197

Gnomad AMR exome

AF:

0.0286

Gnomad ASJ exome

AF:

0.140

Gnomad EAS exome

AF:

0.0000568

Gnomad SAS exome

AF:

0.0167

Gnomad FIN exome

AF:

0.00753

Gnomad NFE exome

AF:

0.0490

Gnomad OTH exome

AF:

0.0508

GnomAD4 exome

AF:

0.0418

AC:

60364

AN:

1445084

Hom.:

1616

Cov.:

AF XY:

0.0418

AC XY:

30056

AN XY:

719330

show subpopulations

Gnomad4 AFR exome

AF:

0.0196

Gnomad4 AMR exome

AF:

0.0312

Gnomad4 ASJ exome

AF:

0.147

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0184

Gnomad4 FIN exome

AF:

0.00950

Gnomad4 NFE exome

AF:

0.0444

Gnomad4 OTH exome

AF:

0.0457

GnomAD4 genome

AF:

0.0350

AC:

5335

AN:

152294

Hom.:

150

Cov.:

AF XY:

0.0326

AC XY:

2431

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0204

Gnomad4 AMR

AF:

0.0374

Gnomad4 ASJ

AF:

0.145

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0182

Gnomad4 FIN

AF:

0.00537

Gnomad4 NFE

AF:

0.0452

Gnomad4 OTH

AF:

0.0487

Alfa

AF:

0.0518

Hom.:

Bravo

AF:

0.0384

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0595

EpiControl

AF:

0.0581

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 08, 2013

- -

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

-0.83

CADD

Benign

3.0

DANN

Benign

0.53

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