chr21-46416836-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006031.6(PCNT):c.6918T>C(p.Ala2306Ala) 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

Publications

2 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: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
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 -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 VariationId is 159643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNT	NM_006031.6	MANE Select	c.6918T>C	p.Ala2306Ala	synonymous	Exon 30 of 47	NP_006022.3
	PCNT	NM_001315529.2		c.6564T>C	p.Ala2188Ala	synonymous	Exon 30 of 47	NP_001302458.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PCNT	ENST00000359568.10	TSL:1 MANE Select	c.6918T>C	p.Ala2306Ala	synonymous	Exon 30 of 47	ENSP00000352572.5
PCNT	ENST00000480896.5	TSL:1	c.6564T>C	p.Ala2188Ala	synonymous	Exon 30 of 47	ENSP00000511989.1
PCNT	ENST00000695558.1		c.6951T>C	p.Ala2317Ala	synonymous	Exon 31 of 48	ENSP00000512015.1

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

GnomAD2 exomes

AF:

0.0379

AC:

8655

AN:

228324

AF XY:

0.0381

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 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

African (AFR)

AF:

0.0196

AC:

655

AN:

33428

American (AMR)

AF:

0.0312

AC:

1394

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

3841

AN:

26088

East Asian (EAS)

AF:

0.000101

AC:

AN:

39690

South Asian (SAS)

AF:

0.0184

AC:

1587

AN:

86184

European-Finnish (FIN)

AF:

0.00950

AC:

363

AN:

38212

Middle Eastern (MID)

AF:

0.0845

AC:

426

AN:

5042

European-Non Finnish (NFE)

AF:

0.0444

AC:

49345

AN:

1111582

Other (OTH)

AF:

0.0457

AC:

2749

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

2943

5886

8830

11773

14716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1784

3568

5352

7136

8920

<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:

0.0350

AC:

5335

AN:

152294

Hom.:

150

Cov.:

AF XY:

0.0326

AC XY:

2431

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0204

AC:

850

AN:

41580

American (AMR)

AF:

0.0374

AC:

572

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

503

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5170

South Asian (SAS)

AF:

0.0182

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00537

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0452

AC:

3077

AN:

68014

Other (OTH)

AF:

0.0487

AC:

103

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

275

550

824

1099

1374

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0513

Hom.:

Bravo

AF:

0.0384

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0595

EpiControl

AF:

0.0581

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Microcephalic osteodysplastic primordial dwarfism type II (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.0

(source)

DANN

Benign

0.53

PhyloP100

0.022

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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

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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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over