NM_000538.4(RFXAP):c.127C>T (p.Gln43Ter) AND MHC class II deficiency

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Apr 24, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000686231.13

Allele description [Variation Report for NM_000538.4(RFXAP):c.127C>T (p.Gln43Ter)]

NM_000538.4(RFXAP):c.127C>T (p.Gln43Ter)

Genes:

LOC130009573:ATAC-STARR-seq lymphoblastoid silent region 5267 [Gene]
RFXAP:regulatory factor X associated protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q13.3

Genomic location:

Preferred name:

NM_000538.4(RFXAP):c.127C>T (p.Gln43Ter)

HGVS:

NC_000013.11:g.36819484C>T
NG_007876.1:g.5283C>T
NM_000538.4:c.127C>TMANE SELECT
NP_000529.1:p.Gln43Ter
NP_000529.1:p.Gln43Ter
LRG_103t1:c.127C>T
LRG_103:g.5283C>T
LRG_103p1:p.Gln43Ter
NC_000013.10:g.37393621C>T
NM_000538.3:c.127C>T

Protein change:

Q43*

Links:

dbSNP: rs1313207845

NCBI 1000 Genomes Browser:

rs1313207845

Molecular consequence:

NM_000538.4:c.127C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: MHC class II deficiency
Synonyms:: BLS, TYPE II; SCID, HLA CLASS II-NEGATIVE; Bare Lymphocyte Syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008855; MedGen: C5447452; Orphanet: 572; OMIM: PS209920

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000813740	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 24, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9118943, 22390233, 28492532
SCV002570640	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Jul 14, 2022)	germline	clinical testing	Citation Link,
SCV003841703	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 23, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31589614, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000813740

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 24, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002570640

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Jul 14, 2022)

germline

clinical testing

Citation Link,

SCV003841703

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 23, 2023)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

RFXAP, a novel subunit of the RFX DNA binding complex is mutated in MHC class II deficiency.

Durand B, Sperisen P, Emery P, Barras E, Zufferey M, Mach B, Reith W.

EMBO J. 1997 Mar 3;16(5):1045-55.

PubMed [citation]

PMID:: 9118943
PMCID:: PMC1169704

Type III bare lymphocyte syndrome associated with a novel RFXAP mutation: a case report.

Gokturk B, Artac H, van Eggermond MJ, van den Elsen P, Reisli İ.

Int J Immunogenet. 2012 Aug;39(4):362-4. doi: 10.1111/j.1744-313X.2012.01105.x. Epub 2012 Mar 6.

PubMed [citation]

PMID:: 22390233

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000813740.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Gln43*) in the RFXAP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RFXAP are known to be pathogenic (PMID: 9118943, 22390233). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with RFXAP-related conditions. ClinVar contains an entry for this variant (Variation ID: 566425). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002570640.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Variant summary: RFXAP c.127C>T (p.Gln43X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.4e-05 in 147392 control chromosomes. To our knowledge, no occurrence of c.127C>T in individuals affected with Bare Lymphocyte Syndrome 2 - RFXAP Related and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From 3billion, SCV003841703.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000566425 / PMID: 31589614). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 20, 2025

ClinVar

Relating variation to medicine