chr21-46380713-G-A

Position:

• chr21-46380713-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006031.6(PCNT):​c.3166-981G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0331 in 152,158 control chromosomes in the GnomAD database, including 144 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 0.033 (144 hom., cov: 30)
• Consequence: PCNT NM_006031.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCNT	NM_006031.6	c.3166-981G>A		intron_variant		ENST00000359568.10
PCNT	NM_001315529.2	c.2812-981G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNT	ENST00000359568.10	c.3166-981G>A		intron_variant		1	NM_006031.6	P2

Frequencies

GnomAD3 genomes AF: 0.0330 AC: 5019 AN: 152040 Hom.: 140 Cov.: 30

Gnomad AFR AF: 0.0772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.0818

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.0325

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

GnomAD4 genome AF: 0.0331 AC: 5039 AN: 152158 Hom.: 144 Cov.: 30 AF XY: 0.0339 AC XY: 2525 AN XY: 74390

Gnomad4 AFR AF: 0.0772

Gnomad4 AMR AF: 0.0198

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.00521

Gnomad4 SAS AF: 0.0817

Gnomad4 FIN AF: 0.0227

Gnomad4 NFE AF: 0.0108

Gnomad4 OTH AF: 0.0373

Alfa AF: 0.0249 Hom.: 12

Bravo AF: 0.0332

Asia WGS AF: 0.0720 AC: 251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.36

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: rs10483082; hg19: chr21-47800628;