21-46431594-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006031.6(PCNT):​c.8130C>G​(p.His2710Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H2710Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PCNT
NM_006031.6 missense

Scores

1
3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.43

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: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1677002).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PCNTNM_006031.6 linkc.8130C>G p.His2710Gln missense_variant Exon 38 of 47 ENST00000359568.10 NP_006022.3 O95613-1
PCNTNM_001315529.2 linkc.7776C>G p.His2592Gln missense_variant Exon 38 of 47 NP_001302458.1 O95613-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PCNTENST00000359568.10 linkc.8130C>G p.His2710Gln missense_variant Exon 38 of 47 1 NM_006031.6 ENSP00000352572.5 O95613-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461730
Hom.:
0
Cov.:
37
AF XY:
0.00000138
AC XY:
1
AN XY:
727146
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53346
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1111932
Other (OTH)
AF:
0.00
AC:
0
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.49
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
4.7
DANN
Benign
0.90
DEOGEN2
Benign
0.25
T
Eigen
Benign
-0.82
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.086
N
LIST_S2
Benign
0.66
T
M_CAP
Benign
0.0076
T
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M
PhyloP100
-1.4
PrimateAI
Uncertain
0.52
T
PROVEAN
Pathogenic
-5.7
D
REVEL
Benign
0.16
Sift
Benign
0.15
T
Sift4G
Benign
0.13
T
Polyphen
1.0
D
Vest4
0.26
MutPred
0.077
Gain of MoRF binding (P = 0.1001);
MVP
0.26
MPC
0.32
ClinPred
0.83
D
GERP RS
-6.8
Varity_R
0.12
gMVP
0.14
Mutation Taster
=72/28
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs373738288; hg19: chr21-47851508; API