dbSNP rs148444313: PCNT:p.Val2311Val (chr21-46418215-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_006031.6(PCNT):c.6933C>T(p.Val2311Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,587,530 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0030 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 27 hom. )

Consequence

PCNT
NM_006031.6 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: -1.02

Publications

3 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 21-46418215-C-T is Benign according to our data. Variant chr21-46418215-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 211876.

BP7

Synonymous conserved (PhyloP=-1.02 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00295 (449/151972) while in subpopulation SAS AF = 0.00581 (28/4818). AF 95% confidence interval is 0.00413. There are 0 homozygotes in GnomAd4. There are 258 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 27 AR gene

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.6933C>T	p.Val2311Val	synonymous	Exon 31 of 47	NP_006022.3
	PCNT	NM_001315529.2		c.6579C>T	p.Val2193Val	synonymous	Exon 31 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.6933C>T	p.Val2311Val	synonymous	Exon 31 of 47	ENSP00000352572.5	O95613-1
PCNT	ENST00000480896.5	TSL:1	c.6579C>T	p.Val2193Val	synonymous	Exon 31 of 47	ENSP00000511989.1	O95613-2
PCNT	ENST00000695558.1		c.6966C>T	p.Val2322Val	synonymous	Exon 32 of 48	ENSP00000512015.1	A0A8Q3SHZ3

Frequencies

GnomAD3 genomes

AF:

0.00292

AC:

444

AN:

151854

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00581

Gnomad FIN

AF:

0.0119

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00301

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00372

AC:

935

AN:

251110

AF XY:

0.00423

show subpopulations

Gnomad AFR exome

AF:

0.00118

Gnomad AMR exome

AF:

0.00182

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0133

Gnomad NFE exome

AF:

0.00268

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00286

AC:

4112

AN:

1435558

Hom.:

Cov.:

AF XY:

0.00319

AC XY:

2282

AN XY:

716150

show subpopulations

African (AFR)

AF:

0.000775

AC:

AN:

32276

American (AMR)

AF:

0.00193

AC:

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.000116

AC:

AN:

25942

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39584

South Asian (SAS)

AF:

0.00809

AC:

693

AN:

85690

European-Finnish (FIN)

AF:

0.0131

AC:

702

AN:

53392

Middle Eastern (MID)

AF:

0.00280

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.00219

AC:

2389

AN:

1088876

Other (OTH)

AF:

0.00330

AC:

196

AN:

59418

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

190

379

569

758

948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<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:

0.00295

AC:

449

AN:

151972

Hom.:

Cov.:

AF XY:

0.00347

AC XY:

258

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.00145

AC:

AN:

41320

American (AMR)

AF:

0.00150

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00581

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0119

AC:

126

AN:

10574

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00301

AC:

205

AN:

67994

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00227

Hom.:

Bravo

AF:

0.00171

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00262

EpiControl

AF:

0.00267

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Microcephalic osteodysplastic primordial dwarfism type II (2)

not specified (1)

PCNT-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.62

(source)

DANN

Benign

0.83

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism

(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

Computational scores

Splicing

Publications

Other links and lift over