NM_000116.5(TAFAZZIN):c.238G>C (p.Gly80Arg) AND 3-Methylglutaconic aciduria type 2

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Oct 29, 2018
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:: RCV000995886.7

Allele description [Variation Report for NM_000116.5(TAFAZZIN):c.238G>C (p.Gly80Arg)]

NM_000116.5(TAFAZZIN):c.238G>C (p.Gly80Arg)

Gene:

TAFAZZIN:tafazzin, phospholipid-lysophospholipid transacylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_000116.5(TAFAZZIN):c.238G>C (p.Gly80Arg)

HGVS:

NC_000023.11:g.154412214G>C
NG_009634.2:g.5680G>C
NG_012884.2:g.4875C>G
NM_000116.5:c.238G>CMANE SELECT
NM_001303465.2:c.292G>C
NM_181311.4:c.238G>C
NM_181312.4:c.238G>C
NM_181313.4:c.238G>C
NP_000107.1:p.Gly80Arg
NP_001290394.1:p.Gly98Arg
NP_851828.1:p.Gly80Arg
NP_851829.1:p.Gly80Arg
NP_851830.1:p.Gly80Arg
LRG_131t1:c.238G>C
LRG_131:g.5680G>C
LRG_131p1:p.Gly80Arg
NC_000023.10:g.153640551G>C
NG_009634.1:g.5675G>C
NM_000116.3:c.238G>C
NR_024048.3:n.543G>C

Protein change:

G80R

Links:

dbSNP: rs1557191170

NCBI 1000 Genomes Browser:

rs1557191170

Molecular consequence:

NM_000116.5:c.238G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001303465.2:c.292G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_181311.4:c.238G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_181312.4:c.238G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_181313.4:c.238G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_024048.3:n.543G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: 3-Methylglutaconic aciduria type 2 (BTHS)
Synonyms:: Barth syndrome; 3-methylglutaconicaciduria type II; MGA type II; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010543; MedGen: C0574083; Orphanet: 111; OMIM: 302060

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001150276	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	criteria provided, single submitter (Classification criteria August 2017)	Likely pathogenic (Oct 29, 2018)	germline	clinical testing	Citation Link,
SCV001571489	Kids Neuroscience Centre, Sydney Children's Hospitals Network	criteria provided, single submitter (Bournazos AM et al. (Genet Med 2021))	Pathogenic	de novo	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

SCV001150276

Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München

criteria provided, single submitter

(Classification criteria August 2017)

Likely pathogenic
(Oct 29, 2018)

germline

clinical testing

Citation Link,

SCV001571489

Kids Neuroscience Centre, Sydney Children's Hospitals Network

criteria provided, single submitter

(Bournazos AM et al. (Genet Med 2021))

Pathogenic

de novo

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	de novo	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Standardized practices for RNA diagnostics using clinically accessible specimens reclassifies 75% of putative splicing variants.

Bournazos AM, Riley LG, Bommireddipalli S, Ades L, Akesson LS, Al-Shinnag M, Alexander SI, Archibald AD, Balasubramaniam S, Berman Y, Beshay V, Boggs K, Bojadzieva J, Brown NJ, Bryen SJ, Buckley MF, Chong B, Davis MR, Dawes R, Delatycki M, Donaldson L, Downie L, et al.

Genet Med. 2022 Jan;24(1):130-145. doi: 10.1016/j.gim.2021.09.001. Epub 2021 Nov 30.

PubMed [citation]

PMID:: 34906502

Details of each submission

From Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München, SCV001150276.1

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

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

From Kids Neuroscience Centre, Sydney Children's Hospitals Network, SCV001571489.2

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

Description

Use of Intron-2 cryptic 5’ splice-site abnormally includes 36 nt of intron-2 into the TAZ pre-mRNA, encoding 12 ectopic amino acids into the tafazzin protein. Exon-2 skipping abnormally removes 129 nucleotides from the TAZ pre-mRNA. This event is in frame, deleting 43 (highly conserved) amino acids from the encoded tafazzin protein. Our RT-PCR results infer splicing outcomes consistent with a damaging effect for the encoded tafazzin protein.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	1	Whole blood; Myocardium	not provided		1	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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