rs61407822

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.2415C>G(p.Ala805Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 1,614,106 control chromosomes in the GnomAD database, including 7,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 3523 hom., cov: 33)

Exomes 𝑓: 0.026 ( 3645 hom. )

Consequence

PCNT
NM_006031.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.146

Publications

4 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=-0.66).

BP6

Variant 21-46363740-C-G is Benign according to our data. Variant chr21-46363740-C-G is described in ClinVar as Benign. ClinVar VariationId is 138616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.146 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 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.2415C>G	p.Ala805Ala	synonymous	Exon 14 of 47	NP_006022.3
	PCNT	NM_001315529.2		c.2061C>G	p.Ala687Ala	synonymous	Exon 14 of 47	NP_001302458.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PCNT	ENST00000359568.10	TSL:1 MANE Select	c.2415C>G	p.Ala805Ala	synonymous	Exon 14 of 47	ENSP00000352572.5
PCNT	ENST00000480896.5	TSL:1	c.2061C>G	p.Ala687Ala	synonymous	Exon 14 of 47	ENSP00000511989.1
PCNT	ENST00000695558.1		c.2415C>G	p.Ala805Ala	synonymous	Exon 14 of 48	ENSP00000512015.1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19579

AN:

152118

Hom.:

3520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.406

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0606

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.00559

Gnomad SAS

AF:

0.0828

Gnomad FIN

AF:

0.0225

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.111

GnomAD2 exomes

AF:

0.0498

AC:

12511

AN:

251384

AF XY:

0.0450

show subpopulations

Gnomad AFR exome

AF:

0.416

Gnomad AMR exome

AF:

0.0331

Gnomad ASJ exome

AF:

0.0151

Gnomad EAS exome

AF:

0.00364

Gnomad FIN exome

AF:

0.0220

Gnomad NFE exome

AF:

0.0128

Gnomad OTH exome

AF:

0.0310

GnomAD4 exome

AF:

0.0265

AC:

38739

AN:

1461870

Hom.:

3645

Cov.:

AF XY:

0.0267

AC XY:

19434

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.428

AC:

14342

AN:

33478

American (AMR)

AF:

0.0358

AC:

1603

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0147

AC:

384

AN:

26136

East Asian (EAS)

AF:

0.00194

AC:

AN:

39700

South Asian (SAS)

AF:

0.0708

AC:

6111

AN:

86258

European-Finnish (FIN)

AF:

0.0203

AC:

1084

AN:

53404

Middle Eastern (MID)

AF:

0.0411

AC:

237

AN:

5766

European-Non Finnish (NFE)

AF:

0.0109

AC:

12164

AN:

1112008

Other (OTH)

AF:

0.0453

AC:

2737

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

1978

3957

5935

7914

9892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

684

1368

2052

2736

3420

<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:

0.129

AC:

19619

AN:

152236

Hom.:

3523

Cov.:

AF XY:

0.126

AC XY:

9384

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.406

AC:

16851

AN:

41516

American (AMR)

AF:

0.0605

AC:

925

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0159

AC:

AN:

3468

East Asian (EAS)

AF:

0.00560

AC:

AN:

5178

South Asian (SAS)

AF:

0.0825

AC:

398

AN:

4824

European-Finnish (FIN)

AF:

0.0225

AC:

239

AN:

10624

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0126

AC:

860

AN:

68010

Other (OTH)

AF:

0.115

AC:

243

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

651

1302

1952

2603

3254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<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:

0.0215

Hom.:

Bravo

AF:

0.143

Asia WGS

AF:

0.0920

AC:

318

AN:

3478

EpiCase

AF:

0.0146

EpiControl

AF:

0.0156

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Microcephalic osteodysplastic primordial dwarfism type II (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.4

(source)

DANN

Benign

0.50

PhyloP100

-0.15

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

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over