chr13-36819401-C-T

Variant names:

Variant summary

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

The NM_000538.4(RFXAP):c.44C>T(p.Ala15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000306 in 1,306,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 8.7e-7 ( 0 hom. )

Consequence

RFXAP
NM_000538.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 0.596

Publications

1 publications found

Variant links:

Genes affected

RFXAP (HGNC:9988): (regulatory factor X associated protein) Major histocompatibility (MHC) class II molecules are transmembrane proteins that have a central role in development and control of the immune system. The protein encoded by this gene, along with regulatory factor X-associated ankyrin-containing protein and regulatory factor-5, forms a complex that binds to the X box motif of certain MHC class II gene promoters and activates their transcription. Once bound to the promoter, this complex associates with the non-DNA-binding factor MHC class II transactivator, which controls the cell type specificity and inducibility of MHC class II gene expression. Mutations in this gene have been linked to bare lymphocyte syndrome type II, complementation group D. Transcript variants utilizing different polyA signals have been found for this gene. [provided by RefSeq, Jul 2008]

RFXAP Gene-Disease associations (from GenCC):

MHC class II deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

RFXAP links:

ENSG00000309469 (HGNC:):

ENSG00000309469 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=0.09277475).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000538.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFXAP	NM_000538.4	MANE Select	c.44C>T	p.Ala15Val	missense	Exon 1 of 3	NP_000529.1	O00287

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFXAP	ENST00000255476.3	TSL:1 MANE Select	c.44C>T	p.Ala15Val	missense	Exon 1 of 3	ENSP00000255476.3	O00287
	ENSG00000309469	ENST00000841309.1		n.122+176G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151964

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

7714

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

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:

8.66e-7

AC:

AN:

1154674

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

553876

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23274

American (AMR)

AF:

0.00

AC:

AN:

8812

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15190

East Asian (EAS)

AF:

0.0000368

AC:

AN:

27180

South Asian (SAS)

AF:

0.00

AC:

AN:

30796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3358

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

965992

Other (OTH)

AF:

0.00

AC:

AN:

47102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152072

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41552

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000195

AC:

AN:

5130

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67928

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

MHC class II deficiency (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.48

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.093

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PhyloP100

0.60

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.73

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Benign

0.18

Polyphen

0.16

Vest4

0.20

MutPred

0.24

Gain of catalytic residue at V18 (P = 0.0037)

MVP

0.055

MPC

1.7

ClinPred

0.58

GERP RS

3.8

PromoterAI

-0.0038

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.14

Mutation Taster

=98/2

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

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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