21-46324213-G-T

Position:

chr21-46324213-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006031.6(PCNT):c.-16G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0555 in 1,606,990 control chromosomes in the GnomAD database, including 2,873 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 211 hom., cov: 35)

Exomes 𝑓: 0.057 ( 2662 hom. )

Consequence

PCNT
NM_006031.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.135

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=-0.71).

BP6

Variant 21-46324213-G-T is Benign according to our data. Variant chr21-46324213-G-T is described in ClinVar as [Benign]. Clinvar id is 138617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46324213-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0645 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.-16G>T		5_prime_UTR_variant	1/47	ENST00000359568.10	NP_006022.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCNT	ENST00000359568.10 linkuse as main transcript	c.-16G>T		5_prime_UTR_variant	1/47	1	NM_006031.6	ENSP00000352572	P2	O95613-1

Frequencies

GnomAD3 genomes

AF:

0.0432

AC:

6577

AN:

152176

Hom.:

212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0263

Gnomad ASJ

AF:

0.0562

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00890

Gnomad FIN

AF:

0.0858

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0661

Gnomad OTH

AF:

0.0402

GnomAD3 exomes

AF:

0.0440

AC:

10480

AN:

238208

Hom.:

270

AF XY:

0.0439

AC XY:

5687

AN XY:

129464

show subpopulations

Gnomad AFR exome

AF:

0.00810

Gnomad AMR exome

AF:

0.0182

Gnomad ASJ exome

AF:

0.0563

Gnomad EAS exome

AF:

0.0000559

Gnomad SAS exome

AF:

0.0136

Gnomad FIN exome

AF:

0.0869

Gnomad NFE exome

AF:

0.0636

Gnomad OTH exome

AF:

0.0471

GnomAD4 exome

AF:

0.0568

AC:

82568

AN:

1454696

Hom.:

2662

Cov.:

AF XY:

0.0557

AC XY:

40258

AN XY:

723282

show subpopulations

Gnomad4 AFR exome

AF:

0.00824

Gnomad4 AMR exome

AF:

0.0203

Gnomad4 ASJ exome

AF:

0.0552

Gnomad4 EAS exome

AF:

0.0000759

Gnomad4 SAS exome

AF:

0.0135

Gnomad4 FIN exome

AF:

0.0853

Gnomad4 NFE exome

AF:

0.0642

Gnomad4 OTH exome

AF:

0.0500

GnomAD4 genome

AF:

0.0432

AC:

6575

AN:

152294

Hom.:

211

Cov.:

AF XY:

0.0423

AC XY:

3152

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.0262

Gnomad4 ASJ

AF:

0.0562

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00911

Gnomad4 FIN

AF:

0.0858

Gnomad4 NFE

AF:

0.0661

Gnomad4 OTH

AF:

0.0397

Alfa

AF:

0.0355

Hom.:

Bravo

AF:

0.0375

Asia WGS

AF:

0.00924

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 31, 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:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

-0.71

CADD

Benign

7.2

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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