rs3788265

Variant names:

• chr21-46413875-G-T
• rs3788265
• NM_006031.6:c.6150+883G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006031.6(PCNT):​c.6150+883G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,202 control chromosomes in the GnomAD database, including 2,750 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2750 hom., cov: 33)
• Consequence: PCNT NM_006031.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006031.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNT	NM_006031.6	MANE Select	c.6150+883G>T		intron	N/A	NP_006022.3
	PCNT	NM_001315529.2		c.5796+883G>T		intron	N/A	NP_001302458.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNT	ENST00000359568.10	TSL:1 MANE Select	c.6150+883G>T		intron	N/A	ENSP00000352572.5
	PCNT	ENST00000480896.5	TSL:1	c.5796+883G>T		intron	N/A	ENSP00000511989.1
	PCNT	ENST00000695558.1		c.6183+883G>T		intron	N/A	ENSP00000512015.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26607 AN: 152084 Hom.: 2753 Cov.: 33

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.193

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.175 AC: 26602 AN: 152202 Hom.: 2750 Cov.: 33 AF XY: 0.175 AC XY: 13051 AN XY: 74410

African (AFR) AF: 0.0745 AC: 3095 AN: 41550

American (AMR) AF: 0.157 AC: 2407 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 806 AN: 3470

East Asian (EAS) AF: 0.400 AC: 2075 AN: 5184

South Asian (SAS) AF: 0.228 AC: 1101 AN: 4822

European-Finnish (FIN) AF: 0.229 AC: 2427 AN: 10584

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13980 AN: 67982

Other (OTH) AF: 0.193 AC: 407 AN: 2110

Alfa AF: 0.183 Hom.: 575

Bravo AF: 0.167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.62
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

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: rs3788265; hg19: chr21-47833789;