rs2839223

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006031.6(PCNT):​c.2111G>C​(p.Gly704Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. G704E) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Consequence

PCNT
NM_006031.6 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.93
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10953671).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PCNTNM_006031.6 linkuse as main transcriptc.2111G>C p.Gly704Ala missense_variant 13/47 ENST00000359568.10 NP_006022.3 O95613-1
PCNTNM_001315529.2 linkuse as main transcriptc.1757G>C p.Gly586Ala missense_variant 13/47 NP_001302458.1 O95613-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PCNTENST00000359568.10 linkuse as main transcriptc.2111G>C p.Gly704Ala missense_variant 13/471 NM_006031.6 ENSP00000352572.5 O95613-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
44
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
17
DANN
Benign
0.88
DEOGEN2
Benign
0.021
T
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.44
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.36
T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
0.75
N
REVEL
Benign
0.16
Sift
Benign
0.059
T
Sift4G
Benign
0.29
T
Polyphen
0.0
B
Vest4
0.14
MutPred
0.067
Loss of ubiquitination at K705 (P = 0.1264);
MVP
0.46
MPC
0.087
ClinPred
0.13
T
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.062
gMVP
0.013

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2839223; hg19: chr21-47777063; API