NM_001025603.2:c.1039T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001025603.2(RFX5):c.1039T>C(p.Ser347Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000737 in 1,613,870 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S347S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 2 hom. )

Consequence

RFX5
NM_001025603.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4O:1

Conservation

PhyloP100: 1.75

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.054139942).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

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	UniProt
RFX5	NM_001025603.2	MANE Select	c.1039T>C	p.Ser347Pro	missense	Exon 11 of 11	NP_001020774.1	P48382-1
RFX5	NM_000449.4		c.1039T>C	p.Ser347Pro	missense	Exon 11 of 11	NP_000440.1	P48382-1
RFX5	NM_001379412.1		c.1039T>C	p.Ser347Pro	missense	Exon 11 of 11	NP_001366341.1	P48382-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RFX5	ENST00000452671.7	TSL:1 MANE Select	c.1039T>C	p.Ser347Pro	missense	Exon 11 of 11	ENSP00000389130.2	P48382-1
RFX5	ENST00000290524.8	TSL:1	c.1039T>C	p.Ser347Pro	missense	Exon 11 of 11	ENSP00000290524.4	P48382-1
RFX5	ENST00000368870.6	TSL:5	c.1039T>C	p.Ser347Pro	missense	Exon 11 of 11	ENSP00000357864.2	P48382-1

Frequencies

GnomAD3 genomes

AF:

0.000440

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

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:

0.000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000356

AC:

AN:

250074

AF XY:

0.000443

show subpopulations

Gnomad AFR exome

AF:

0.000191

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000742

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000768

AC:

1123

AN:

1461632

Hom.:

Cov.:

AF XY:

0.000761

AC XY:

553

AN XY:

727106

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33474

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000982

AC:

1092

AN:

1111898

Other (OTH)

AF:

0.000315

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

148

222

296

370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000440

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41538

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000882

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

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:

0.000562

Hom.:

Bravo

AF:

0.000423

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000321

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.000474

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

MHC class II deficiency (4)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

0.057

Eigen_PC

Benign

0.067

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.69

M_CAP

Benign

0.018

MetaRNN

Benign

0.054

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

1.8

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.70

REVEL

Benign

0.13

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0090

Polyphen

0.77

Vest4

0.28

MVP

0.76

MPC

0.38

ClinPred

0.096

GERP RS

2.6

Varity_R

0.19

gMVP

0.41

Mutation Taster

=75/25

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over