rs3788265

Positions:

• chr21-46413875-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCNT	NM_006031.6	c.6150+883G>T		intron_variant		ENST00000359568.10
PCNT	NM_001315529.2	c.5796+883G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNT	ENST00000359568.10	c.6150+883G>T		intron_variant		1	NM_006031.6	P2

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

Gnomad4 AFR AF: 0.0745

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.193

Alfa AF: 0.186 Hom.: 573

Bravo AF: 0.167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.62

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: rs3788265; hg19: chr21-47833789;