chr20-5119342-T-C

Variant names:

• chr20-5119342-T-C
• rs25405
• NM_182649.2:c.221+236A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_182649.2(PCNA):​c.221+236A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,180 control chromosomes in the GnomAD database, including 2,576 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 (2576 hom., cov: 33)
• Consequence: PCNA NM_182649.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 5 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]

ENSG00000302261 (HGNC:):

PCNA-AS1 (HGNC:37184): (PCNA antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNA	NM_182649.2	MANE Select	c.221+236A>G		intron	N/A	NP_872590.1	P12004
	PCNA	NM_002592.2		c.221+236A>G		intron	N/A	NP_002583.1	P12004
	PCNA-AS1	NR_028370.1		n.-244T>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNA	ENST00000379143.10	TSL:1 MANE Select	c.221+236A>G		intron	N/A	ENSP00000368438.5	P12004
	PCNA	ENST00000379160.3	TSL:5	c.221+236A>G		intron	N/A	ENSP00000368458.3	P12004
	PCNA	ENST00000875657.1		c.221+236A>G		intron	N/A	ENSP00000545716.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23531 AN: 152062 Hom.: 2570 Cov.: 33

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0561

Gnomad FIN AF: 0.0596

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.155 AC: 23564 AN: 152180 Hom.: 2576 Cov.: 33 AF XY: 0.151 AC XY: 11236 AN XY: 74408

African (AFR) AF: 0.305 AC: 12658 AN: 41514

American (AMR) AF: 0.109 AC: 1663 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 510 AN: 3468

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5170

South Asian (SAS) AF: 0.0563 AC: 272 AN: 4830

European-Finnish (FIN) AF: 0.0596 AC: 633 AN: 10616

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

European-Non Finnish (NFE) AF: 0.108 AC: 7342 AN: 67982

Other (OTH) AF: 0.152 AC: 321 AN: 2110

Alfa AF: 0.144 Hom.: 293

Bravo AF: 0.164

Asia WGS AF: 0.0440 AC: 156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.81
PhyloP100		0.079
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: rs25405; hg19: chr20-5099988;