rs1555945478

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The ENST00000359568.10(PCNT):c.442_519delGTCAGTGACCACCCACCAGAACAGCATGGGATGTTCACAGTCAGTGACCACCCACCAGAACAGCGTGGGATGTTCACA(p.Val148_Thr173del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 116,800 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000017 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000078 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PCNT
ENST00000359568.10 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 1.28

Publications

0 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: Uncertain_significance. The variant received 2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in ENST00000359568.10.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000359568.10. 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.442_519delGTCAGTGACCACCCACCAGAACAGCATGGGATGTTCACAGTCAGTGACCACCCACCAGAACAGCGTGGGATGTTCACA	p.Val148_Thr173del	conservative_inframe_deletion	Exon 3 of 47	NP_006022.3
	PCNT	NM_001315529.2		c.88_165delGTCAGTGACCACCCACCAGAACAGCATGGGATGTTCACAGTCAGTGACCACCCACCAGAACAGCGTGGGATGTTCACA	p.Val30_Thr55del	conservative_inframe_deletion	Exon 3 of 47	NP_001302458.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PCNT	ENST00000359568.10	TSL:1 MANE Select	c.442_519delGTCAGTGACCACCCACCAGAACAGCATGGGATGTTCACAGTCAGTGACCACCCACCAGAACAGCGTGGGATGTTCACA	p.Val148_Thr173del	conservative_inframe_deletion	Exon 3 of 47	ENSP00000352572.5
PCNT	ENST00000480896.5	TSL:1	c.88_165delGTCAGTGACCACCCACCAGAACAGCATGGGATGTTCACAGTCAGTGACCACCCACCAGAACAGCGTGGGATGTTCACA	p.Val30_Thr55del	conservative_inframe_deletion	Exon 3 of 47	ENSP00000511989.1
PCNT	ENST00000695558.1		c.442_519delGTCAGTGACCACCCACCAGAACAGCATGGGATGTTCACAGTCAGTGACCACCCACCAGAACAGCGTGGGATGTTCACA	p.Val148_Thr173del	conservative_inframe_deletion	Exon 3 of 48	ENSP00000512015.1

Frequencies

GnomAD3 genomes

AF:

0.0000171

AC:

AN:

116800

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000372

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000413

AC:

AN:

241924

AF XY:

0.00000762

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000912

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000782

AC:

AN:

1407332

Hom.:

AF XY:

0.00000429

AC XY:

AN XY:

699364

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31030

American (AMR)

AF:

0.00

AC:

AN:

42670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24220

East Asian (EAS)

AF:

0.00

AC:

AN:

38838

South Asian (SAS)

AF:

0.00

AC:

AN:

81556

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5452

European-Non Finnish (NFE)

AF:

0.00000836

AC:

AN:

1076750

Other (OTH)

AF:

0.0000349

AC:

AN:

57302

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000471512), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.352

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000171

AC:

AN:

116800

Hom.:

Cov.:

AF XY:

0.0000175

AC XY:

AN XY:

57064

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

29170

American (AMR)

AF:

0.00

AC:

AN:

12186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2746

East Asian (EAS)

AF:

0.00

AC:

AN:

4598

South Asian (SAS)

AF:

0.00

AC:

AN:

3698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

246

European-Non Finnish (NFE)

AF:

0.0000372

AC:

AN:

53822

Other (OTH)

AF:

0.00

AC:

AN:

1592

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

PCNT-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Mutation Taster

=144/56

polymorphism

(source)

Splicing

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

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over