NM_001199107.2(TBC1D24):c.457G>A (p.Glu153Lys) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Jan 22, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000189685.22

Allele description [Variation Report for NM_001199107.2(TBC1D24):c.457G>A (p.Glu153Lys)]

NM_001199107.2(TBC1D24):c.457G>A (p.Glu153Lys)

Gene:

TBC1D24:TBC1 domain family member 24 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_001199107.2(TBC1D24):c.457G>A (p.Glu153Lys)

Other names:

p.E153K:GAG>AAG

HGVS:

NC_000016.10:g.2496605G>A
NG_028170.1:g.26460G>A
NM_001199107.2:c.457G>AMANE SELECT
NM_020705.3:c.457G>A
NP_001186036.1:p.Glu153Lys
NP_065756.1:p.Glu153Lys
NC_000016.9:g.2546606G>A
NM_001199107.1:c.457G>A
NM_020705.2:c.457G>A

Protein change:

E153K

Links:

dbSNP: rs376712059

NCBI 1000 Genomes Browser:

rs376712059

Molecular consequence:

NM_001199107.2:c.457G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020705.3:c.457G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000243331	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Jan 22, 2024)	germline	clinical testing	Citation Link,
SCV003819865	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 14, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004229318	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Likely pathogenic (Dec 13, 2022)	unknown	clinical testing	PubMed (10) [See all records that cite these PMIDs] 28428906, 28292732, 27281533, 26371875, 25769375, 33619735, 31216405, 28726039, 32004315, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000243331

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Jan 22, 2024)

germline

clinical testing

Citation Link,

SCV003819865

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 14, 2022)

germline

clinical testing

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

SCV004229318

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Likely pathogenic
(Dec 13, 2022)

unknown

clinical testing

PubMed (10)
[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	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

TBC1D24 Mutations in a Sibship with Multifocal Polymyoclonus.

Ngoh A, Bras J, Guerreiro R, McTague A, Ng J, Meyer E, Chong WK, Boyd S, MacLellan L, Kirkpatrick M, Kurian MA.

Tremor Other Hyperkinet Mov (N Y). 2017;7:452. doi: 10.7916/D8Q52VBV.

PubMed [citation]

PMID:: 28428906
PMCID:: PMC5395678

See all PubMed Citations (11)

Details of each submission

From GeneDx, SCV000243331.19

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

Description

Identified with a second TBC1D24 variant on the opposite allele (in trans) in siblings with nonsyndromic hearing loss in published literature (PMID: 26371875); authors propose that the second variant may be hypomorphic, resulting in a milder phenotype; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24291220, 27259978, 25769375, 28428906, 32004315, 28292732, 27652284, 27281533, 31216405, 33619735, 34852372, Timpanaro2021[Review], 28726039, 33986365, 35350397, 37538433, Mehdaoui2023[casereport], Vetri2024[casereport], 26371875)

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

From Revvity Omics, Revvity, SCV003819865.2

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Athena Diagnostics, SCV004229318.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with epileptic encephalopathy and appears to segregate with disease in at least one family with infantile myoclonic epilepsy. Computational tools predict that this variant is damaging.

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

Last Updated: Aug 25, 2024

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