NM_004208.4(AIFM1):c.1265G>A (p.Arg422Gln) AND Deafness, X-linked 5

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 25, 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:: RCV000149865.6

Allele description [Variation Report for NM_004208.4(AIFM1):c.1265G>A (p.Arg422Gln)]

NM_004208.4(AIFM1):c.1265G>A (p.Arg422Gln)

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.1265G>A (p.Arg422Gln)

HGVS:

NC_000023.11:g.130136085C>T
NG_013217.1:g.34749G>A
NM_001130846.4:c.248G>A
NM_001130847.4:c.*493G>A
NM_004208.4:c.1265G>AMANE SELECT
NM_145812.3:c.1253G>A
NP_001124318.2:p.Arg83Gln
NP_004199.1:p.Arg422Gln
NP_665811.1:p.Arg418Gln
NC_000023.10:g.129270060C>T
NM_004208.3:c.1265G>A
NR_132647.2:n.1510G>A
O95831:p.Arg422Gln

Protein change:

R418Q; ARG422GLN

Links:

UniProtKB: O95831#VAR_076214; OMIM: 300169.0007; dbSNP: rs724160021

NCBI 1000 Genomes Browser:

rs724160021

Molecular consequence:

NM_001130847.4:c.*493G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001130846.4:c.248G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004208.4:c.1265G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_145812.3:c.1253G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_132647.2:n.1510G>A - 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
SCV000196719	Deafness Gene Diagnosis, Xijing Hospital	no assertion criteria provided	Likely pathogenic	unknown	clinical testing
SCV000257356	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 2015)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV003920981	Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 25, 2023)	maternal	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000196719

Deafness Gene Diagnosis, Xijing Hospital

no assertion criteria provided

Likely pathogenic

unknown

clinical testing

SCV000257356

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 2015)

germline

literature only

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

SCV003920981

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 25, 2023)

maternal

clinical testing

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	maternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
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

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 Deafness Gene Diagnosis, Xijing Hospital, SCV000196719.2

#	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, SCV000257356.2

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

Description

In 3 affected brothers from a Chinese family (family 2423) with X-linked deafness-5 (DFNX5; 300614), Zong et al. (2015) identified a hemizygous c.1265G-A transition (c.1265G-A, NM_004208.3) in exon 12 of the AIFM1 gene, resulting in an arg422-to-gln (R422Q) substitution. The variant was not found in the Exome Sequencing Project or 1000 Genomes Project databases or in 500 Chinese controls. 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

From Equipe Genetique des Anomalies du Developpement, Université de Bourgogne, SCV003920981.1

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

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

Last Updated: May 16, 2025

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