rs138868039

Variant names:

• chr21-46431865-G-A
• rs138868039
• NM_006031.6:c.8401G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-46431865-G-A
• chr21-46431865-G-C
• chr21-46431865-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006031.6(PCNT):​c.8401G>A​(p.Val2801Met) 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. 14/22 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. V2801L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: PCNT NM_006031.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.12
• Publications: 7 publications found

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

ACMG classification

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=0.2566474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNT	NM_006031.6	c.8401G>A	p.Val2801Met	missense_variant	Exon 38 of 47	ENST00000359568.10	NP_006022.3
PCNT	NM_001315529.2	c.8047G>A	p.Val2683Met	missense_variant	Exon 38 of 47		NP_001302458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNT	ENST00000359568.10	c.8401G>A	p.Val2801Met	missense_variant	Exon 38 of 47	1	NM_006031.6	ENSP00000352572.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.081
Eigen_PC	Benign	-0.0093
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.1
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.11
Sift	Benign	0.095	T
Sift4G	Benign	0.066	T
Polyphen		0.99	D
Vest4		0.21
MutPred		0.22		Gain of MoRF binding (P = 0.0958);
MVP		0.34
MPC		0.39
ClinPred		0.61	D
GERP RS		3.5
Varity_R		0.035
gMVP		0.079
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs138868039; hg19: chr21-47851779;