NM_006031.6:c.8258G>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.8258G>A(p.Arg2753His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0546 in 1,611,716 control chromosomes in the GnomAD database, including 2,754 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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. R2753L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.048 ( 223 hom., cov: 33)

Exomes 𝑓: 0.055 ( 2531 hom. )

Consequence

PCNT
NM_006031.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.465

Publications

20 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=0.001970321).

BP6

Variant 21-46431722-G-A is Benign according to our data. Variant chr21-46431722-G-A is described in ClinVar as Benign. ClinVar VariationId is 138610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0622 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.8258G>A	p.Arg2753His	missense	Exon 38 of 47	NP_006022.3
	PCNT	NM_001315529.2		c.7904G>A	p.Arg2635His	missense	Exon 38 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.8258G>A	p.Arg2753His	missense	Exon 38 of 47	ENSP00000352572.5	O95613-1
PCNT	ENST00000480896.5	TSL:1	c.7904G>A	p.Arg2635His	missense	Exon 38 of 47	ENSP00000511989.1	O95613-2
PCNT	ENST00000695558.1		c.8291G>A	p.Arg2764His	missense	Exon 39 of 48	ENSP00000512015.1	A0A8Q3SHZ3

Frequencies

GnomAD3 genomes

AF:

0.0479

AC:

7285

AN:

152204

Hom.:

224

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0265

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0335

Gnomad ASJ

AF:

0.0711

Gnomad EAS

AF:

0.000965

Gnomad SAS

AF:

0.00890

Gnomad FIN

AF:

0.0848

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0638

Gnomad OTH

AF:

0.0497

GnomAD2 exomes

AF:

0.0462

AC:

11341

AN:

245422

AF XY:

0.0457

show subpopulations

Gnomad AFR exome

AF:

0.0271

Gnomad AMR exome

AF:

0.0221

Gnomad ASJ exome

AF:

0.0724

Gnomad EAS exome

AF:

0.000331

Gnomad FIN exome

AF:

0.0879

Gnomad NFE exome

AF:

0.0626

Gnomad OTH exome

AF:

0.0516

GnomAD4 exome

AF:

0.0553

AC:

80734

AN:

1459394

Hom.:

2531

Cov.:

AF XY:

0.0543

AC XY:

39407

AN XY:

726016

show subpopulations

African (AFR)

AF:

0.0250

AC:

836

AN:

33462

American (AMR)

AF:

0.0240

AC:

1068

AN:

44568

Ashkenazi Jewish (ASJ)

AF:

0.0711

AC:

1856

AN:

26118

East Asian (EAS)

AF:

0.000580

AC:

AN:

39670

South Asian (SAS)

AF:

0.0140

AC:

1204

AN:

86218

European-Finnish (FIN)

AF:

0.0833

AC:

4306

AN:

51672

Middle Eastern (MID)

AF:

0.0327

AC:

188

AN:

5752

European-Non Finnish (NFE)

AF:

0.0613

AC:

68134

AN:

1111596

Other (OTH)

AF:

0.0517

AC:

3119

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

4906

9813

14719

19626

24532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2462

4924

7386

9848

12310

<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:

0.0479

AC:

7291

AN:

152322

Hom.:

223

Cov.:

AF XY:

0.0474

AC XY:

3528

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0266

AC:

1106

AN:

41574

American (AMR)

AF:

0.0334

AC:

512

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.0711

AC:

247

AN:

3472

East Asian (EAS)

AF:

0.000967

AC:

AN:

5170

South Asian (SAS)

AF:

0.00911

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0848

AC:

901

AN:

10624

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0638

AC:

4338

AN:

68016

Other (OTH)

AF:

0.0491

AC:

104

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

368

736

1104

1472

1840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0552

Hom.:

300

Bravo

AF:

0.0434

TwinsUK

AF:

0.0556

AC:

206

ALSPAC

AF:

0.0602

AC:

232

ESP6500AA

AF:

0.0329

AC:

145

ESP6500EA

AF:

0.0624

AC:

537

ExAC

AF:

0.0461

AC:

5596

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Microcephalic osteodysplastic primordial dwarfism type II (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.7

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.24

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

0.47

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.031

Sift

Benign

0.082

Sift4G

Uncertain

0.041

Polyphen

0.98

Vest4

0.064

MPC

0.42

ClinPred

0.011

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.043

gMVP

0.18

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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