Genetic Variant RFX4:p.Arg29Ser (chr12-106608838-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_213594.3(RFX4):c.85C>A(p.Arg29Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000671 in 149,052 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)

Consequence

RFX4
NM_213594.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.69

Publications

1 publications found

Variant links:

Genes affected

RFX4 (HGNC:9985): (regulatory factor X4) This gene is a member of the regulatory factor X gene family, which encodes transcription factors that contain a highly-conserved winged helix DNA binding domain. The protein encoded by this gene is structurally related to regulatory factors X1, X2, X3, and X5. It has been shown to interact with itself as well as with regulatory factors X2 and X3, but it does not interact with regulatory factor X1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

RFX4 links:

ENSG00000257545 (HGNC:58967):

ENSG00000257545 links:

LOC100287944 (HGNC:):

LOC100287944 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213594.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RFX4	NM_213594.3	MANE Select	c.85C>A	p.Arg29Ser	missense	Exon 2 of 18	NP_998759.1	Q33E94-1
RFX4	NM_001206691.2		c.112C>A	p.Arg38Ser	missense	Exon 2 of 18	NP_001193620.1	Q33E94-2
LOC100287944	NR_040246.1		n.143-101028G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RFX4	ENST00000392842.6	TSL:1 MANE Select	c.85C>A	p.Arg29Ser	missense	Exon 2 of 18	ENSP00000376585.1	Q33E94-1
RFX4	ENST00000357881.8	TSL:1	c.112C>A	p.Arg38Ser	missense	Exon 2 of 18	ENSP00000350552.4	Q33E94-2
RFX4	ENST00000536688.5	TSL:1	n.217C>A		non_coding_transcript_exon	Exon 2 of 15

Frequencies

GnomAD3 genomes

AF:

0.00000671

AC:

AN:

149052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000248

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000671

AC:

AN:

149052

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72402

show subpopulations

African (AFR)

AF:

0.0000248

AC:

AN:

40266

American (AMR)

AF:

0.00

AC:

AN:

14816

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5108

South Asian (SAS)

AF:

0.00

AC:

AN:

4754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9742

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67650

Other (OTH)

AF:

0.00

AC:

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.060

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.053

MetaRNN

Uncertain

0.63

MetaSVM

Benign

-0.59

MutationAssessor

Benign

0.0

PhyloP100

5.7

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.14

REVEL

Uncertain

0.33

Sift

Benign

0.054

Sift4G

Benign

0.97

Polyphen

0.99

Vest4

0.85

MutPred

0.16

Gain of phosphorylation at R29 (P = 0.0267)

MVP

0.043

MPC

1.0

ClinPred

0.97

GERP RS

4.8

Varity_R

0.33

gMVP

0.66

Mutation Taster

=4/96

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over