rs61735811

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.5634C>T(p.Asp1878Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0542 in 1,612,720 control chromosomes in the GnomAD database, including 2,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 224 hom., cov: 34)

Exomes 𝑓: 0.055 ( 2474 hom. )

Consequence

PCNT
NM_006031.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.18

Publications

9 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 21-46411707-C-T is Benign according to our data. Variant chr21-46411707-C-T is described in ClinVar as Benign. ClinVar VariationId is 95338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.18 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0614 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.5634C>T	p.Asp1878Asp	synonymous	Exon 28 of 47	NP_006022.3
	PCNT	NM_001315529.2		c.5280C>T	p.Asp1760Asp	synonymous	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.5634C>T	p.Asp1878Asp	synonymous	Exon 28 of 47	ENSP00000352572.5	O95613-1
PCNT	ENST00000480896.5	TSL:1	c.5280C>T	p.Asp1760Asp	synonymous	Exon 28 of 47	ENSP00000511989.1	O95613-2
PCNT	ENST00000695558.1		c.5667C>T	p.Asp1889Asp	synonymous	Exon 29 of 48	ENSP00000512015.1	A0A8Q3SHZ3

Frequencies

GnomAD3 genomes

AF:

0.0486

AC:

7393

AN:

152218

Hom.:

225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0308

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0336

Gnomad ASJ

AF:

0.0709

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00869

Gnomad FIN

AF:

0.0841

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0630

Gnomad OTH

AF:

0.0492

GnomAD2 exomes

AF:

0.0457

AC:

11130

AN:

243466

AF XY:

0.0453

show subpopulations

Gnomad AFR exome

AF:

0.0312

Gnomad AMR exome

AF:

0.0216

Gnomad ASJ exome

AF:

0.0720

Gnomad EAS exome

AF:

0.000503

Gnomad FIN exome

AF:

0.0855

Gnomad NFE exome

AF:

0.0613

Gnomad OTH exome

AF:

0.0503

GnomAD4 exome

AF:

0.0548

AC:

80074

AN:

1460384

Hom.:

2474

Cov.:

AF XY:

0.0538

AC XY:

39060

AN XY:

726540

show subpopulations

African (AFR)

AF:

0.0284

AC:

951

AN:

33468

American (AMR)

AF:

0.0234

AC:

1048

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0711

AC:

1858

AN:

26122

East Asian (EAS)

AF:

0.000328

AC:

AN:

39692

South Asian (SAS)

AF:

0.0136

AC:

1173

AN:

86256

European-Finnish (FIN)

AF:

0.0830

AC:

4331

AN:

52172

Middle Eastern (MID)

AF:

0.0326

AC:

188

AN:

5768

European-Non Finnish (NFE)

AF:

0.0606

AC:

67422

AN:

1111824

Other (OTH)

AF:

0.0512

AC:

3090

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

4791

9583

14374

19166

23957

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2442

4884

7326

9768

12210

<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:

0.0486

AC:

7396

AN:

152336

Hom.:

224

Cov.:

AF XY:

0.0482

AC XY:

3589

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0308

AC:

1282

AN:

41588

American (AMR)

AF:

0.0335

AC:

513

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0709

AC:

246

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5190

South Asian (SAS)

AF:

0.00890

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0841

AC:

893

AN:

10622

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0629

AC:

4280

AN:

68004

Other (OTH)

AF:

0.0487

AC:

103

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

366

732

1097

1463

1829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0505

Hom.:

108

Bravo

AF:

0.0442

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0549

EpiControl

AF:

0.0545

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Microcephalic osteodysplastic primordial dwarfism type II (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.28

(source)

DANN

Benign

0.53

PhyloP100

-2.2

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

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