rs17345528

Variant names:

• chr3-101575986-C-A
• rs17345528
• NM_020357.3:c.64+1707C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020357.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNP	NM_020357.3	MANE Select	c.64+1707C>A		intron	N/A	NP_065090.1
	PCNP	NM_001320398.1		c.64+1707C>A		intron	N/A	NP_001307327.1
	PCNP	NM_001320399.1		c.-123+1707C>A		intron	N/A	NP_001307328.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNP	ENST00000265260.8	TSL:1 MANE Select	c.64+1707C>A		intron	N/A	ENSP00000265260.3
	PCNP	ENST00000469941.5	TSL:1	c.-91+1707C>A		intron	N/A	ENSP00000470810.1
	PCNP	ENST00000460231.5	TSL:1	n.64+1707C>A		intron	N/A	ENSP00000419390.1

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

African (AFR) AF: 0.159 AC: 6607 AN: 41460

American (AMR) AF: 0.215 AC: 3286 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1080 AN: 3468

East Asian (EAS) AF: 0.286 AC: 1475 AN: 5158

South Asian (SAS) AF: 0.197 AC: 950 AN: 4816

European-Finnish (FIN) AF: 0.289 AC: 3043 AN: 10518

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16708 AN: 67974

Other (OTH) AF: 0.217 AC: 459 AN: 2112

Alfa AF: 0.233 Hom.: 2023

Bravo AF: 0.216

Asia WGS AF: 0.200 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.34
PhyloP100		-0.97
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: rs17345528; hg19: chr3-101294830; COSMIC: COSV54575578; COSMIC: COSV54575578;