chr20-5115125-C-G

Variant names:

• chr20-5115125-C-G
• rs3626
• NM_182649.2:c.*158G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182649.2(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 NM_182649.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.508
• Publications: 21 publications found

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]

PCNA Gene-Disease associations (from GenCC):

• ataxia-telangiectasia-like disorder 2

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182649.2. 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
	PCNA	NM_182649.2	MANE Select	c.*158G>C		3_prime_UTR	Exon 6 of 6	NP_872590.1
	PCNA	NM_002592.2		c.*158G>C		3_prime_UTR	Exon 7 of 7	NP_002583.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNA	ENST00000379143.10	TSL:1 MANE Select	c.*158G>C		3_prime_UTR	Exon 6 of 6	ENSP00000368438.5
	PCNA	ENST00000379160.3	TSL:5	c.*158G>C		3_prime_UTR	Exon 7 of 7	ENSP00000368458.3

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

African (AFR) AF: 0.297 AC: 3312 AN: 11166

American (AMR) AF: 0.0901 AC: 1275 AN: 14148

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 1851 AN: 12302

East Asian (EAS) AF: 0.0000705 AC: 2 AN: 28380

South Asian (SAS) AF: 0.0633 AC: 2352 AN: 37156

European-Finnish (FIN) AF: 0.0690 AC: 2053 AN: 29744

Middle Eastern (MID) AF: 0.142 AC: 253 AN: 1782

European-Non Finnish (NFE) AF: 0.108 AC: 26842 AN: 247766

Other (OTH) AF: 0.117 AC: 2730 AN: 23326

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

African (AFR) AF: 0.295 AC: 12230 AN: 41456

American (AMR) AF: 0.108 AC: 1646 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 512 AN: 3468

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0564 AC: 272 AN: 4822

European-Finnish (FIN) AF: 0.0598 AC: 632 AN: 10560

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7357 AN: 67986

Other (OTH) AF: 0.150 AC: 316 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.63
PhyloP100		0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3626; hg19: chr20-5095771;