dbSNP rs61735810: PCNT:p.Ala1914Ala (chr21-46411815-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006031.6(PCNT):c.5742G>A(p.Ala1914Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00274 in 1,579,220 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 45 hom., cov: 34)

Exomes 𝑓: 0.0015 ( 46 hom. )

Consequence

PCNT
NM_006031.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.48

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: 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=-0.89).

BP6

Variant 21-46411815-G-A is Benign according to our data. Variant chr21-46411815-G-A is described in ClinVar as Benign. ClinVar VariationId is 159624.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.48 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0144 (2199/152338) while in subpopulation AFR AF = 0.0499 (2077/41586). AF 95% confidence interval is 0.0482. There are 45 homozygotes in GnomAd4. There are 1005 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 45 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.5742G>A	p.Ala1914Ala	synonymous	Exon 28 of 47	NP_006022.3
	PCNT	NM_001315529.2		c.5388G>A	p.Ala1796Ala	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.5742G>A	p.Ala1914Ala	synonymous	Exon 28 of 47	ENSP00000352572.5	O95613-1
PCNT	ENST00000480896.5	TSL:1	c.5388G>A	p.Ala1796Ala	synonymous	Exon 28 of 47	ENSP00000511989.1	O95613-2
PCNT	ENST00000695558.1		c.5775G>A	p.Ala1925Ala	synonymous	Exon 29 of 48	ENSP00000512015.1	A0A8Q3SHZ3

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

2193

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0500

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00812

GnomAD2 exomes

AF:

0.00378

AC:

713

AN:

188380

AF XY:

0.00299

show subpopulations

Gnomad AFR exome

AF:

0.0576

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.000451

Gnomad EAS exome

AF:

0.000629

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000245

Gnomad OTH exome

AF:

0.00139

GnomAD4 exome

AF:

0.00149

AC:

2128

AN:

1426882

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

912

AN XY:

708154

show subpopulations

African (AFR)

AF:

0.0498

AC:

1634

AN:

32840

American (AMR)

AF:

0.00271

AC:

111

AN:

40962

Ashkenazi Jewish (ASJ)

AF:

0.000508

AC:

AN:

25598

East Asian (EAS)

AF:

0.000261

AC:

AN:

38316

South Asian (SAS)

AF:

0.0000473

AC:

AN:

84478

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40780

Middle Eastern (MID)

AF:

0.00129

AC:

AN:

5408

European-Non Finnish (NFE)

AF:

0.000140

AC:

154

AN:

1099298

Other (OTH)

AF:

0.00329

AC:

195

AN:

59202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

128

256

384

512

640

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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:

0.0144

AC:

2199

AN:

152338

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1005

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0499

AC:

2077

AN:

41586

American (AMR)

AF:

0.00529

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68024

Other (OTH)

AF:

0.00803

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

113

226

339

452

565

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0244

Hom.:

241

Bravo

AF:

0.0166

Asia WGS

AF:

0.00231

AC:

AN:

3476

ClinVar

ClinVar submissions

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 (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.062

(source)

DANN

Benign

0.60

PhyloP100

-5.5

Mutation Taster

=98/2

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

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