NM_024417.5(FDXR):c.463C>T (p.Arg155Trp) AND Auditory neuropathy-optic atrophy syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 23, 2023
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:: RCV003152758.1

Allele description [Variation Report for NM_024417.5(FDXR):c.463C>T (p.Arg155Trp)]

NM_024417.5(FDXR):c.463C>T (p.Arg155Trp)

Gene:

FDXR:ferredoxin reductase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q25.1

Genomic location:

Preferred name:

NM_024417.5(FDXR):c.463C>T (p.Arg155Trp)

HGVS:

NC_000017.11:g.74866175G>A
NM_001258012.4:c.592C>T
NM_001258013.4:c.556C>T
NM_001258014.4:c.439C>T
NM_001258015.3:c.343C>T
NM_001258016.3:c.307C>T
NM_004110.6:c.463C>T
NM_024417.5:c.463C>TMANE SELECT
NP_001244941.2:p.Arg198Trp
NP_001244942.2:p.Arg186Trp
NP_001244943.2:p.Arg147Trp
NP_001244944.1:p.Arg115Trp
NP_001244945.2:p.Arg103Trp
NP_004101.3:p.Arg155Trp
NP_077728.3:p.Arg155Trp
NC_000017.10:g.72862297G>A
NM_004110.3:c.463C>T
NM_024417.4:c.463C>T
NR_047576.3:n.613C>T

Protein change:

R103W; ARG155TRP

Links:

OMIM: 103270.0008; dbSNP: rs752675360

NCBI 1000 Genomes Browser:

rs752675360

Molecular consequence:

NM_001258012.4:c.592C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258013.4:c.556C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258014.4:c.439C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258015.3:c.343C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258016.3:c.307C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004110.6:c.463C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_024417.5:c.463C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_047576.3:n.613C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Auditory neuropathy-optic atrophy syndrome
Synonyms:: AUDITORY NEUROPATHY AND OPTIC ATROPHY; MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 9A
Identifiers:: MONDO: MONDO:0060582; MedGen: C4521678; OMIM: 617717

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
SCV003841954	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 23, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30250212, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003841954

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely 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	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Biallelic mutations in FDXR cause neurodegeneration associated with inflammation.

Slone J, Peng Y, Chamberlin A, Harris B, Kaylor J, McDonald MT, Lemmon M, El-Dairi MA, Tchapyjnikov D, Gonzalez-Krellwitz LA, Sellars EA, McConkie-Rosell A, Reinholdt LG, Huang T.

J Hum Genet. 2018 Dec;63(12):1211-1222. doi: 10.1038/s10038-018-0515-y. Epub 2018 Sep 25.

PubMed [citation]

PMID:: 30250212
PMCID:: PMC6451867

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From 3billion, SCV003841954.1

#	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%). Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (3Cnet: 0.75). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000983267 / PMID: 30250212). Therefore, this variant is classified as Likely 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: Sep 16, 2024

ClinVar

Relating variation to medicine