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

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: May 8, 2023
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:: RCV000637296.6

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

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

HGVS:

NC_000023.11:g.154412214G>A
NG_009634.2:g.5680G>A
NG_012884.2:g.4875C>T
NM_000116.5:c.238G>AMANE SELECT
NM_001303465.2:c.292G>A
NM_181311.4:c.238G>A
NM_181312.4:c.238G>A
NM_181313.4:c.238G>A
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>A
LRG_131:g.5680G>A
LRG_131p1:p.Gly80Arg
NC_000023.10:g.153640551G>A
NG_009634.1:g.5675G>A
NM_000116.4:c.238G>A
NR_024048.3:n.543G>A

Protein change:

G80R

Links:

dbSNP: rs1557191170

NCBI 1000 Genomes Browser:

rs1557191170

Molecular consequence:

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

Recent activity

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SRX5193088 (1)
SRA
Homo sapiens zinc finger protein 138 (ZNF138), transcript variant 8, non-coding ...
Homo sapiens zinc finger protein 138 (ZNF138), transcript variant 8, non-coding RNA
gi|1531792098|ref|NR_073391.2|

Nucleotide
Homo sapiens zinc finger protein 138 (ZNF138), transcript variant 18, non-coding...
Homo sapiens zinc finger protein 138 (ZNF138), transcript variant 18, non-coding RNA
gi|1531792101|ref|NR_160270.1|

Nucleotide
Kelch domain containing 8A [Mus musculus]
Kelch domain containing 8A [Mus musculus]
gi|15029824|gb|AAH11135.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000758746	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 8, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17576681, 9536098, 21300850, 24342716, 28492532
SCV003935938	Molecular Diagnostics Lab, Nemours Children's Health, Delaware	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 22, 2020)	maternal	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24342716, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000758746

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 8, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV003935938

Molecular Diagnostics Lab, Nemours Children's Health, Delaware

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jul 22, 2020)

maternal

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	maternal	yes	2	not provided	not provided	2	not provided	clinical testing

Citations

PubMed

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000758746.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with altered splicing resulting in multiple RNA products (PMID: 24342716). Experimental studies have shown that this variant affects TAZ function (PMID: 21300850). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 531184). This variant has been observed in individual(s) with Barth syndrome (PMID: 24342716). This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 80 of the TAZ mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the TAZ protein. This variant also falls at the last nucleotide of exon 2, which is part of the consensus splice site for this exon.

#	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 Molecular Diagnostics Lab, Nemours Children's Health, Delaware, SCV003935938.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing (GTR000500853.3)	PubMed (2)
2	not provided	1	not provided	not provided	clinical testing (GTR000500853.3)	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	maternal	yes	1	blood	not provided	(GTR000500853.3)	1	not provided	not provided	not provided
2	maternal	yes	1	blood	not provided	(GTR000500853.3)	1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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