rs9315266

Positions:

• chr13-33892190-C-T

Variant summary

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

The XM_017020680.3(RFC3):​c.*3001C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0698 in 152,086 control chromosomes in the GnomAD database, including 606 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 0.070 (606 hom., cov: 32)
• Consequence: RFC3 XM_017020680.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168

Genes affected

RFC3 (HGNC:9971): (replication factor C subunit 3) The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase epsilon requires the accessory proteins proliferating cell nuclear antigen (PCNA) and replication factor C (RFC). RFC, also named activator 1, is a protein complex consisting of five distinct subunits of 140, 40, 38, 37, and 36 kDa. This gene encodes the 38 kDa subunit. This subunit is essential for the interaction between the 140 kDa subunit and the core complex that consists of the 36, 37, and 40 kDa subunits. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFC3	XM_017020680.3	c.*3001C>T		3_prime_UTR_variant	9/9
RFC3	XM_047430489.1	c.*1151C>T		3_prime_UTR_variant	10/10
RFC3	NM_181558.3	c.879+56973C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFC3	ENST00000434425.5	c.879+56973C>T		intron_variant		5
RFC3	ENST00000616236.1	c.273+56973C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0697 AC: 10588 AN: 151966 Hom.: 600 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0264

Gnomad OTH AF: 0.0578

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

GnomAD4 genome AF: 0.0698 AC: 10615 AN: 152086 Hom.: 606 Cov.: 32 AF XY: 0.0714 AC XY: 5306 AN XY: 74344

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.0559

Gnomad4 ASJ AF: 0.0297

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0215

Gnomad4 NFE AF: 0.0264

Gnomad4 OTH AF: 0.0577

Alfa AF: 0.0339 Hom.: 173

Bravo AF: 0.0737

Asia WGS AF: 0.119 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9315266; hg19: chr13-34466327;