NM_000631.5(NCF4):c.179G>A (p.Arg60His) AND Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 15, 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:: RCV000648868.6

Allele description [Variation Report for NM_000631.5(NCF4):c.179G>A (p.Arg60His)]

NM_000631.5(NCF4):c.179G>A (p.Arg60His)

Genes:

NCF4-AS1:NCF4 antisense RNA 1 [Gene - HGNC]
NCF4:neutrophil cytosolic factor 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q12.3

Genomic location:

Preferred name:

NM_000631.5(NCF4):c.179G>A (p.Arg60His)

HGVS:

NC_000022.11:g.36864980G>A
NG_023400.1:g.8993G>A
NM_000631.5:c.179G>AMANE SELECT
NM_013416.4:c.179G>A
NP_000622.2:p.Arg60His
NP_038202.2:p.Arg60His
NP_038202.2:p.Arg60His
LRG_159t1:c.179G>A
LRG_159:g.8993G>A
LRG_159p1:p.Arg60His
NC_000022.10:g.37261022G>A
NM_013416.3:c.179G>A

Protein change:

R60H

Links:

dbSNP: rs369847561

NCBI 1000 Genomes Browser:

rs369847561

Molecular consequence:

NM_000631.5:c.179G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_013416.4:c.179G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3
Synonyms:: CGD, AUTOSOMAL RECESSIVE CYTOCHROME b-POSITIVE, TYPE III; GRANULOMATOUS DISEASE, CHRONIC, DUE TO NCF4 DEFICIENCY; Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0013507; MedGen: C3151409; Orphanet: 379; OMIM: 613960

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000770689	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 15, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31027832, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000770689

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 15, 2022)

germline

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

Citations

PubMed

Early Onset Granulomatous Colitis Associated with a Mutation in NCF4 Resolved with Hematopoietic Stem Cell Transplantation.

Wright M, Chandrakasan S, Okou DT, Yin H, Jurickova I, Denson LA, Kugathasan S.

J Pediatr. 2019 Jul;210:220-225. doi: 10.1016/j.jpeds.2019.03.042. Epub 2019 Apr 23.

PubMed [citation]

PMID:: 31027832
PMCID:: PMC8415091

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000770689.5

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

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 60 of the NCF4 protein (p.Arg60His). This variant is present in population databases (rs369847561, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of NCF4-related condition (PMID: 31027832). ClinVar contains an entry for this variant (Variation ID: 539179). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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