NM_000397.4(CYBB):c.169G>T (p.Ala57Ser) AND Granulomatous disease, chronic, X-linked

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 31, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003084665.3

Allele description [Variation Report for NM_000397.4(CYBB):c.169G>T (p.Ala57Ser)]

NM_000397.4(CYBB):c.169G>T (p.Ala57Ser)

Gene:

CYBB:cytochrome b-245 beta chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp21.1

Genomic location:

Preferred name:

NM_000397.4(CYBB):c.169G>T (p.Ala57Ser)

HGVS:

NC_000023.11:g.37783517G>T
NG_009065.1:g.8501G>T
NM_000397.4:c.169G>TMANE SELECT
NP_000388.2:p.Ala57Ser
NP_000388.2:p.Ala57Ser
LRG_53t1:c.169G>T
LRG_53:g.8501G>T
LRG_53p1:p.Ala57Ser
NC_000023.10:g.37642770G>T
NM_000397.3:c.169G>T

Protein change:

A57S

Molecular consequence:

NM_000397.4:c.169G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Granulomatous disease, chronic, X-linked
Synonyms:: CYTOCHROME b-NEGATIVE GRANULOMATOUS DISEASE, CHRONIC, X-LINKED; GRANULOMATOUS DISEASE, CHRONIC, X-LINKED, SOMATIC MOSAIC
Identifiers:: MONDO: MONDO:0010600; MedGen: C1844376; Orphanet: 379; OMIM: 306400

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003479237	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Aug 31, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 8101486, 10914676, 21659519, 30470980, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003479237

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Aug 31, 2022)

germline

clinical testing

PubMed (5)
[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

Citations

PubMed

A newly recognized point mutation in the cytochrome b558 heavy chain gene replacing alanine57 by glutamic acid, in a patient with cytochrome b positive X-linked chronic granulomatous disease.

Ariga T, Sakiyama Y, Tomizawa K, Imajoh-Ohmi S, Kanegasaki S, Matsumoto S.

Eur J Pediatr. 1993 Jun;152(6):469-72.

PubMed [citation]

PMID:: 8101486

Statistical and mutational analysis of chronic granulomatous disease in Japan with special reference to gp91-phox and p22-phox deficiency.

Ishibashi F, Nunoi H, Endo F, Matsuda I, Kanegasaki S.

Hum Genet. 2000 May;106(5):473-81.

PubMed [citation]

PMID:: 10914676

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003479237.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CYBB protein function. This variant has not been reported in the literature in individuals affected with CYBB-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 57 of the CYBB protein (p.Ala57Ser). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Ala57 amino acid residue in CYBB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8101486, 10914676, 21659519, 30470980). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.

#	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

Last Updated: Sep 29, 2024

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