dbSNP rs2233851: RFX5:p.Arg197Pro (chr1-151343848-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001025603.2(RFX5):c.590G>C(p.Arg197Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. R197Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

RFX5
NM_001025603.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.63

Publications

0 publications found

Variant links:

Genes affected

RFX5 (HGNC:9986): (regulatory factor X5) A lack of MHC-II expression results in a severe immunodeficiency syndrome called MHC-II deficiency, or the bare lymphocyte syndrome (BLS; MIM 209920). At least 4 complementation groups have been identified in B-cell lines established from patients with BLS. The molecular defects in complementation groups B, C, and D all lead to a deficiency in RFX, a nuclear protein complex that binds to the X box of MHC-II promoters. The lack of RFX binding activity in complementation group C results from mutations in the RFX5 gene encoding the 75-kD subunit of RFX (Steimle et al., 1995). RFX5 is the fifth member of the growing family of DNA-binding proteins sharing a novel and highly characteristic DNA-binding domain called the RFX motif. Multiple alternatively spliced transcript variants have been found but the full-length natures of only two have been determined. [provided by RefSeq, Jul 2008]

RFX5 links:

RFX5-AS1 (HGNC:40503): (RFX5 antisense RNA 1)

RFX5-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30520862).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025603.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RFX5	NM_001025603.2	MANE Select	c.590G>C	p.Arg197Pro	missense	Exon 9 of 11	NP_001020774.1
RFX5	NM_000449.4		c.590G>C	p.Arg197Pro	missense	Exon 9 of 11	NP_000440.1
RFX5	NM_001379412.1		c.590G>C	p.Arg197Pro	missense	Exon 9 of 11	NP_001366341.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RFX5	ENST00000452671.7	TSL:1 MANE Select	c.590G>C	p.Arg197Pro	missense	Exon 9 of 11	ENSP00000389130.2
RFX5	ENST00000290524.8	TSL:1	c.590G>C	p.Arg197Pro	missense	Exon 9 of 11	ENSP00000290524.4
RFX5	ENST00000368870.6	TSL:5	c.590G>C	p.Arg197Pro	missense	Exon 9 of 11	ENSP00000357864.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.72

M_CAP

Benign

0.048

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.5

PhyloP100

3.6

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.7

REVEL

Benign

0.061

Sift

Uncertain

0.020

Sift4G

Uncertain

0.030

Polyphen

1.0

Vest4

0.35

MutPred

0.28

Gain of catalytic residue at P196 (P = 0.0119)

MVP

0.84

MPC

0.72

ClinPred

0.89

GERP RS

3.9

Varity_R

0.30

gMVP

0.72

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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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