NM_001393500.2(TOMT):c.467del (p.Ile156fs) AND Autosomal recessive nonsyndromic hearing loss 63

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 1, 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:: RCV002283829.8

Allele description [Variation Report for NM_001393500.2(TOMT):c.467del (p.Ile156fs)]

NM_001393500.2(TOMT):c.467del (p.Ile156fs)

Genes:

ANAPC15:anaphase promoting complex subunit 15 [Gene - OMIM - HGNC]
LRTOMT:leucine rich transmembrane and O-methyltransferase domain containing [Gene - OMIM - HGNC]
TOMT:transmembrane O-methyltransferase [Gene - HGNC]

Variant type:

Deletion

Cytogenetic location:

11q13.4

Genomic location:

Preferred name:

NM_001393500.2(TOMT):c.467del (p.Ile156fs)

HGVS:

NC_000011.10:g.72108615del
NG_021423.1:g.33280del
NM_001145308.5:c.566del
NM_001145309.4:c.566del
NM_001145310.4:c.446del
NM_001330321.2:c.319-1010del
NM_001393427.1:c.319-1010del
NM_001393428.1:c.319-1010del
NM_001393429.1:c.319-1010del
NM_001393430.1:c.319-1010del
NM_001393431.1:c.319-1010del
NM_001393443.1:c.*204del
NM_001393444.1:c.*204del
NM_001393445.1:c.*204del
NM_001393459.1:c.64-1010del
NM_001393500.2:c.467delMANE SELECT
NP_001138780.1:p.Ile189Thrfs
NP_001138780.1:p.Ile189fs
NP_001138781.1:p.Ile189fs
NP_001138782.1:p.Ile149fs
NP_001380429.1:p.Ile156fs
NC_000011.9:g.71819661del
NM_001145308.4:c.566delT
NR_171687.1:n.828del

Protein change:

I149fs

Molecular consequence:

NM_001393443.1:c.*204del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001393444.1:c.*204del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001393445.1:c.*204del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001145308.5:c.566del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001145309.4:c.566del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001145310.4:c.446del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001393500.2:c.467del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330321.2:c.319-1010del - intron variant - [Sequence Ontology: SO:0001627]
NM_001393427.1:c.319-1010del - intron variant - [Sequence Ontology: SO:0001627]
NM_001393428.1:c.319-1010del - intron variant - [Sequence Ontology: SO:0001627]
NM_001393429.1:c.319-1010del - intron variant - [Sequence Ontology: SO:0001627]
NM_001393430.1:c.319-1010del - intron variant - [Sequence Ontology: SO:0001627]
NM_001393431.1:c.319-1010del - intron variant - [Sequence Ontology: SO:0001627]
NM_001393459.1:c.64-1010del - intron variant - [Sequence Ontology: SO:0001627]
NR_171687.1:n.828del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Autosomal recessive nonsyndromic hearing loss 63
Synonyms:: Deafness, autosomal recessive 63
Identifiers:: MONDO: MONDO:0012670; MedGen: C1969621; Orphanet: 90636; OMIM: 611451

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002572946	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25788562, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002572946

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 1, 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	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Novel mutations in LRTOMT associated with moderate progressive hearing loss in autosomal recessive inheritance.

Ichinose A, Moteki H, Hattori M, Nishio SY, Usami S.

Ann Otol Rhinol Laryngol. 2015 May;124 Suppl 1:142S-7S. doi: 10.1177/0003489415575043. Epub 2015 Mar 18.

PubMed [citation]

PMID:: 25788562

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, SCV002572946.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	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: 0.003%). It is predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by more than 10%. The variant has been reported to be associated with LRTOMT-related disorder (PMID: 25788562 / 3billion dataset). 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	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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