rs3626

Positions:

• chr20-5115125-C-G

Variant summary

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

The ENST00000379143.10(PCNA):​c.*158G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 557,836 control chromosomes in the GnomAD database, including 4,984 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 0.15 (2435 hom., cov: 33)
  • Exomes 𝑓: 0.10 (2549 hom.)
• Consequence: PCNA ENST00000379143.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.508

Genes affected

PCNA (HGNC:8729): (proliferating cell nuclear antigen) The protein encoded by this gene is found in the nucleus and is a cofactor of DNA polymerase delta. The encoded protein acts as a homotrimer and helps increase the processivity of leading strand synthesis during DNA replication. In response to DNA damage, this protein is ubiquitinated and is involved in the RAD6-dependent DNA repair pathway. Two transcript variants encoding the same protein have been found for this gene. Pseudogenes of this gene have been described on chromosome 4 and on the X chromosome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCNA	NM_182649.2	c.*158G>C		3_prime_UTR_variant	6/6	ENST00000379143.10	NP_872590.1
PCNA	NM_002592.2	c.*158G>C		3_prime_UTR_variant	7/7		NP_002583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCNA	ENST00000379143.10	c.*158G>C		3_prime_UTR_variant	6/6	1	NM_182649.2	ENSP00000368438	P1
PCNA	ENST00000379160.3	c.*158G>C		3_prime_UTR_variant	7/7	5		ENSP00000368458	P1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23099 AN: 151948 Hom.: 2431 Cov.: 33

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0562

Gnomad FIN AF: 0.0598

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.100 AC: 40670 AN: 405770 Hom.: 2549 Cov.: 5 AF XY: 0.0972 AC XY: 20858 AN XY: 214540

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.0901

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.0000705

Gnomad4 SAS exome AF: 0.0633

Gnomad4 FIN exome AF: 0.0690

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.152 AC: 23128 AN: 152066 Hom.: 2435 Cov.: 33 AF XY: 0.149 AC XY: 11046 AN XY: 74332

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0564

Gnomad4 FIN AF: 0.0598

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.150

Alfa AF: 0.135 Hom.: 241

Bravo AF: 0.161

Asia WGS AF: 0.0440 AC: 154 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3626; hg19: chr20-5095771;