rs17345528

Positions:

• chr3-101575986-C-A

Variant summary

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

The NM_020357.3(PCNP):​c.64+1707C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 151,966 control chromosomes in the GnomAD database, including 4,045 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 0.22 (4045 hom., cov: 32)
• Consequence: PCNP NM_020357.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.969

Genes affected

PCNP (HGNC:30023): (PEST proteolytic signal containing nuclear protein) Involved in proteasome-mediated ubiquitin-dependent protein catabolic process and protein ubiquitination. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

PCNP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCNP	NM_020357.3	c.64+1707C>A		intron_variant		ENST00000265260.8	NP_065090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCNP	ENST00000265260.8	c.64+1707C>A		intron_variant		1	NM_020357.3	ENSP00000265260.3

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33811 AN: 151848 Hom.: 4048 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.223 AC: 33824 AN: 151966 Hom.: 4045 Cov.: 32 AF XY: 0.225 AC XY: 16707 AN XY: 74260

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.217

Alfa AF: 0.234 Hom.: 1690

Bravo AF: 0.216

Asia WGS AF: 0.200 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.34

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: rs17345528; hg19: chr3-101294830; COSMIC: COSV54575578; COSMIC: COSV54575578;