21-46411952-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006031.6(PCNT):c.5879G>A(p.Arg1960Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,597,508 control chromosomes in the GnomAD database, including 230 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1960W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.020 ( 115 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 115 hom. )

Consequence

PCNT
NM_006031.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.123

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

microcephalic osteodysplastic primordial dwarfism type II
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet
Moyamoya disease
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp

PCNT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021196902).

BP6

Variant 21-46411952-G-A is Benign according to our data. Variant chr21-46411952-G-A is described in ClinVar as Benign. ClinVar VariationId is 159626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006031.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNT	NM_006031.6	MANE Select	c.5879G>A	p.Arg1960Gln	missense	Exon 28 of 47	NP_006022.3
	PCNT	NM_001315529.2		c.5525G>A	p.Arg1842Gln	missense	Exon 28 of 47	NP_001302458.1	O95613-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCNT	ENST00000359568.10	TSL:1 MANE Select	c.5879G>A	p.Arg1960Gln	missense	Exon 28 of 47	ENSP00000352572.5	O95613-1
PCNT	ENST00000480896.5	TSL:1	c.5525G>A	p.Arg1842Gln	missense	Exon 28 of 47	ENSP00000511989.1	O95613-2
PCNT	ENST00000695558.1		c.5912G>A	p.Arg1971Gln	missense	Exon 29 of 48	ENSP00000512015.1	A0A8Q3SHZ3

Frequencies

GnomAD3 genomes

AF:

0.0200

AC:

3044

AN:

152192

Hom.:

116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0693

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00687

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.0144

GnomAD2 exomes

AF:

0.00516

AC:

1145

AN:

222012

AF XY:

0.00360

show subpopulations

Gnomad AFR exome

AF:

0.0709

Gnomad AMR exome

AF:

0.00343

Gnomad ASJ exome

AF:

0.000105

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000371

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.00224

AC:

3232

AN:

1445198

Hom.:

115

Cov.:

AF XY:

0.00195

AC XY:

1402

AN XY:

719320

show subpopulations

African (AFR)

AF:

0.0749

AC:

2499

AN:

33374

American (AMR)

AF:

0.00369

AC:

164

AN:

44452

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26034

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39550

South Asian (SAS)

AF:

0.000105

AC:

AN:

85804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40324

Middle Eastern (MID)

AF:

0.00377

AC:

AN:

4776

European-Non Finnish (NFE)

AF:

0.000266

AC:

295

AN:

1110908

Other (OTH)

AF:

0.00410

AC:

246

AN:

59976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

199

399

598

798

997

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

258

344

430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0200

AC:

3046

AN:

152310

Hom.:

115

Cov.:

AF XY:

0.0186

AC XY:

1387

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0692

AC:

2876

AN:

41572

American (AMR)

AF:

0.00686

AC:

105

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000441

AC:

AN:

68014

Other (OTH)

AF:

0.0142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

143

286

430

573

716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00399

Hom.:

Bravo

AF:

0.0237

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0552

AC:

241

ESP6500EA

AF:

0.000234

AC:

ExAC

AF:

0.00595

AC:

715

Asia WGS

AF:

0.00520

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Microcephalic osteodysplastic primordial dwarfism type II (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.54

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.024

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

PhyloP100

-0.12

PrimateAI

Benign

0.27

PROVEAN

Benign

0.61

REVEL

Benign

0.029

Sift

Benign

0.36

Sift4G

Benign

0.90

Polyphen

0.29

Vest4

0.18

MVP

0.25

MPC

0.10

ClinPred

0.0033

GERP RS

-8.5

Varity_R

0.016

gMVP

0.057

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over