4-39302312-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002913.5(RFC1):c.2501C>G(p.Ala834Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,612,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
RFC1
NM_002913.5 missense
NM_002913.5 missense
Scores
1
3
13
Clinical Significance
Conservation
PhyloP100: 5.67
Genes affected
RFC1 (HGNC:9969): (replication factor C subunit 1) This gene encodes the large subunit of replication factor C, a five subunit DNA polymerase accessory protein, which is a DNA-dependent ATPase required for eukaryotic DNA replication and repair. The large subunit acts as an activator of DNA polymerases, binds to the 3' end of primers, and promotes coordinated synthesis of both strands. It may also have a role in telomere stability. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Mar 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.078351736).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RFC1 | NM_002913.5 | c.2501C>G | p.Ala834Gly | missense_variant | 19/25 | ENST00000349703.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RFC1 | ENST00000349703.7 | c.2501C>G | p.Ala834Gly | missense_variant | 19/25 | 1 | NM_002913.5 | P4 | |
RFC1 | ENST00000381897.5 | c.2504C>G | p.Ala835Gly | missense_variant | 19/25 | 1 | A2 | ||
RFC1 | ENST00000505077.1 | n.433C>G | non_coding_transcript_exon_variant | 4/5 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251298Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135816
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460442Hom.: 0 Cov.: 30 AF XY: 0.00000826 AC XY: 6AN XY: 726634
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74354
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 03, 2023 | The c.2504C>G (p.A835G) alteration is located in exon 19 (coding exon 19) of the RFC1 gene. This alteration results from a C to G substitution at nucleotide position 2504, causing the alanine (A) at amino acid position 835 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;B
Vest4
MutPred
0.30
.;Gain of catalytic residue at A835 (P = 0.0372);
MVP
MPC
0.17
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at