rs2839223

Positions:

• chr21-46357148-G-C
• chr21-46357148-G-A
• chr21-46357148-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.93

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 (HGNC:):

ACMG classification

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
PCNT	NM_006031.6	c.2111G>C	p.Gly704Ala	missense_variant	13/47	ENST00000359568.10	NP_006022.3
PCNT	NM_001315529.2	c.1757G>C	p.Gly586Ala	missense_variant	13/47		NP_001302458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCNT	ENST00000359568.10	c.2111G>C	p.Gly704Ala	missense_variant	13/47	1	NM_006031.6	ENSP00000352572.5

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

Other links and lift over

dbSNP: rs2839223; hg19: chr21-47777063;