chr21-46418293-T-C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7

The NM_006031.6(PCNT):​c.7011T>C​(p.Asp2337Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000234 in 1,582,188 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00015 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000098 ( 0 hom. )

Consequence

PCNT
NM_006031.6 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.354

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
Variant 21-46418293-T-C is Benign according to our data. Variant chr21-46418293-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 159648.We mark this variant Likely_benign, oryginal submission is: [Conflicting_classifications_of_pathogenicity].
BP7
Synonymous conserved (PhyloP=0.354 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PCNTNM_006031.6 linkc.7011T>C p.Asp2337Asp synonymous_variant Exon 31 of 47 ENST00000359568.10 NP_006022.3 O95613-1
PCNTNM_001315529.2 linkc.6657T>C p.Asp2219Asp synonymous_variant Exon 31 of 47 NP_001302458.1 O95613-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PCNTENST00000359568.10 linkc.7011T>C p.Asp2337Asp synonymous_variant Exon 31 of 47 1 NM_006031.6 ENSP00000352572.5 O95613-1

Frequencies

GnomAD3 genomes
AF:
0.000145
AC:
22
AN:
152230
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000531
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000319
AC:
8
AN:
251066
AF XY:
0.00000736
show subpopulations
Gnomad AFR exome
AF:
0.000433
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:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000979
AC:
14
AN:
1429840
Hom.:
0
Cov.:
26
AF XY:
0.00000701
AC XY:
5
AN XY:
713366
show subpopulations
African (AFR)
AF:
0.000305
AC:
10
AN:
32750
American (AMR)
AF:
0.00
AC:
0
AN:
44688
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25950
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39566
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85568
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53400
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5694
European-Non Finnish (NFE)
AF:
0.00000277
AC:
3
AN:
1082978
Other (OTH)
AF:
0.0000169
AC:
1
AN:
59246
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.439
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000151
AC:
23
AN:
152348
Hom.:
0
Cov.:
33
AF XY:
0.0000940
AC XY:
7
AN XY:
74500
show subpopulations
African (AFR)
AF:
0.000553
AC:
23
AN:
41578
American (AMR)
AF:
0.00
AC:
0
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5190
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10622
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68036
Other (OTH)
AF:
0.00
AC:
0
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.484
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000164
Hom.:
0
Bravo
AF:
0.000106

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Microcephalic osteodysplastic primordial dwarfism type II Uncertain:1
Feb 08, 2013
Genetic Services Laboratory, University of Chicago
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

PCNT-related disorder Benign:1
Jan 15, 2023
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1
Apr 08, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
CADD
Benign
0.56
DANN
Benign
0.67
PhyloP100
0.35
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Other links and lift over

dbSNP: rs138506849; hg19: chr21-47838207; API