NM_021830.5(TWNK):c.1597G>A (p.Ala533Thr) AND Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 12, 2018
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:: RCV001105994.4

Allele description [Variation Report for NM_021830.5(TWNK):c.1597G>A (p.Ala533Thr)]

NM_021830.5(TWNK):c.1597G>A (p.Ala533Thr)

Gene:

TWNK:twinkle mtDNA helicase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q24.31

Genomic location:

Preferred name:

NM_021830.5(TWNK):c.1597G>A (p.Ala533Thr)

HGVS:

NC_000010.11:g.100990873G>A
NG_011646.1:g.1643C>T
NG_012624.1:g.8338G>A
NM_001163812.2:c.1597G>A
NM_001163813.2:c.235G>A
NM_001163814.2:c.235G>A
NM_001368275.1:c.235G>A
NM_021830.5:c.1597G>AMANE SELECT
NP_001157284.1:p.Ala533Thr
NP_001157285.1:p.Ala79Thr
NP_001157286.1:p.Ala79Thr
NP_001355204.1:p.Ala79Thr
NP_068602.2:p.Ala533Thr
NC_000010.10:g.102750630G>A
NC_000010.10:g.102750630G>A
NM_021830.4:c.1597G>A
NR_160738.1:n.2385G>A
NR_160739.1:n.545G>A
NR_160740.1:n.2203G>A
NR_160741.1:n.2203G>A
NR_160742.1:n.2323G>A

Protein change:

A533T

Links:

dbSNP: rs139124415

NCBI 1000 Genomes Browser:

rs139124415

Molecular consequence:

NM_001163812.2:c.1597G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001163813.2:c.235G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001163814.2:c.235G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001368275.1:c.235G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_021830.5:c.1597G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_160738.1:n.2385G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160739.1:n.545G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160740.1:n.2203G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160741.1:n.2203G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160742.1:n.2323G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO)
Synonyms:: SENSORY ATAXIC NEUROPATHY WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE; Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome; Epilepsy, progressive myoclonic, type 5
Identifiers:: MONDO: MONDO:0011835; MedGen: C1843851; OMIM: 607459

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001263018	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Jan 12, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001263018

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Jan 12, 2018)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001263018.1

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

#	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

Last Updated: Jan 13, 2025

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