NM_004208.4(AIFM1):c.1030C>T (p.Leu344Phe) AND Deafness, X-linked 5

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Aug 1, 2015
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000149862.4

Allele description [Variation Report for NM_004208.4(AIFM1):c.1030C>T (p.Leu344Phe)]

NM_004208.4(AIFM1):c.1030C>T (p.Leu344Phe)

Genes:

RAB33A:RAB33A, member RAS oncogene family [Gene - OMIM - HGNC]
AIFM1:apoptosis inducing factor mitochondria associated 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq26.1

Genomic location:

Preferred name:

NM_004208.4(AIFM1):c.1030C>T (p.Leu344Phe)

Other names:

AIFM1, LEU344PHE (rs184474885)

HGVS:

NC_000023.11:g.130137123G>A
NG_013217.1:g.33711C>T
NM_001130846.4:c.13C>T
NM_001130847.4:c.*258C>T
NM_004208.4:c.1030C>TMANE SELECT
NM_145812.3:c.1018C>T
NP_001124318.2:p.Leu5Phe
NP_004199.1:p.Leu344Phe
NP_665811.1:p.Leu340Phe
NC_000023.10:g.129271098G>A
NM_004208.3:c.1030C>T
NR_132647.2:n.1275C>T
O95831:p.Leu344Phe

Protein change:

L340F; LEU344PHE

Links:

UniProtKB: O95831#VAR_076212; OMIM: 300169.0004; dbSNP: rs184474885

NCBI 1000 Genomes Browser:

rs184474885

Molecular consequence:

NM_001130847.4:c.*258C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001130846.4:c.13C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004208.4:c.1030C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_145812.3:c.1018C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_132647.2:n.1275C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Deafness, X-linked 5 (DFNX5)
Synonyms:: AUDITORY NEUROPATHY, X-LINKED, 1, WITH PERIPHERAL SENSORY NEUROPATHY; DEAFNESS, X-LINKED 5, WITH PERIPHERAL NEUROPATHY
Identifiers:: MedGen: C1845095; Orphanet: 139583; OMIM: 300614

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000196716	Deafness Gene Diagnosis, Xijing Hospital	no assertion criteria provided	Likely pathogenic	unknown	clinical testing
SCV000257353	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 2015)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000196716

Deafness Gene Diagnosis, Xijing Hospital

no assertion criteria provided

Likely pathogenic

unknown

clinical testing

SCV000257353

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 2015)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	yes	1	not provided	not provided	183	no	clinical testing

Citations

PubMed

Mutations in apoptosis-inducing factor cause X-linked recessive auditory neuropathy spectrum disorder.

Zong L, Guan J, Ealy M, Zhang Q, Wang D, Wang H, Zhao Y, Shen Z, Campbell CA, Wang F, Yang J, Sun W, Lan L, Ding D, Xie L, Qi Y, Lou X, Huang X, Shi Q, Chang S, Xiong W, Yin Z, et al.

J Med Genet. 2015 Aug;52(8):523-31. doi: 10.1136/jmedgenet-2014-102961. Epub 2015 May 18.

PubMed [citation]

PMID:: 25986071
PMCID:: PMC4518735

Details of each submission

From Deafness Gene Diagnosis, Xijing Hospital, SCV000196716.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	no	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	183	blood	not provided		1	not provided	not provided	not provided

From OMIM, SCV000257353.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 2 Chinese brothers (family 0223) with X-linked deafness-5 (DFNX5; 300614), Zong et al. (2015) identified a hemizygous c.1030C-T transition (rs184474885) in exon 10 of the AIFM1 gene, resulting in a leu344-to-phe (L344F) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was annotated in the dbSNP (build 141) database at a very low frequency (0.0005), but was not found in 500 Chinese controls. Screening for AIFM1 mutations in 93 unrelated patients with sporadic auditory neuropathy revealed that 3 additional unrelated patients carried the L344F mutation. Functional studies of the variant were not performed.

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

Last Updated: May 16, 2025

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