Genetic Variant RFC5:p.Gln9Pro (chr12-118016853-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007370.7(RFC5):c.26A>C(p.Gln9Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q9R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RFC5
NM_007370.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.807

Publications

0 publications found

Variant links:

Genes affected

RFC5 (HGNC:9973): (replication factor C subunit 5) This gene encodes the smallest subunit of the replication factor C complex, which consists of five distinct subunits (140, 40, 38, 37, and 36 kDa) and is required for DNA replication. This subunit interacts with the C-terminal region of proliferating cell nuclear antigen and is required to open and load proliferating cell nuclear antigen onto DNA during S phase. It is a member of the AAA+ (ATPases associated with various cellular activities) ATPase family and forms a core complex with the 38 and 40 kDa subunits that possesses DNA-dependent ATPase activity. A related pseudogene has been identified on chromosome 9. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

RFC5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.089726865).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007370.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RFC5	NM_007370.7	MANE Select	c.26A>C	p.Gln9Pro	missense	Exon 1 of 11	NP_031396.1	P40937-1
RFC5	NM_001206801.3		c.26A>C	p.Gln9Pro	missense	Exon 1 of 11	NP_001193730.1
RFC5	NM_001130113.3		c.-97A>C		5_prime_UTR	Exon 1 of 12	NP_001123585.1	P40937-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RFC5	ENST00000454402.7	TSL:1 MANE Select	c.26A>C	p.Gln9Pro	missense	Exon 1 of 11	ENSP00000408295.2	P40937-1
RFC5	ENST00000900837.1		c.26A>C	p.Gln9Pro	missense	Exon 2 of 12	ENSP00000570896.1
RFC5	ENST00000900836.1		c.26A>C	p.Gln9Pro	missense	Exon 2 of 12	ENSP00000570895.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248060

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461310

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726972

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86194

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111772

Other (OTH)

AF:

0.00

AC:

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.088

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.47

M_CAP

Benign

0.0099

MetaRNN

Benign

0.090

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

0.81

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.010

REVEL

Benign

0.044

Sift

Benign

0.030

Sift4G

Benign

0.25

Polyphen

0.0

Vest4

0.29

MutPred

0.31

Gain of glycosylation at Q9 (P = 0.0169)

MVP

0.28

MPC

0.48

ClinPred

0.24

GERP RS

3.5

PromoterAI

-0.021

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.18

gMVP

0.66

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over