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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:
2

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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000758746Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(May 8, 2023)
germlineclinical testing

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

SCV003935938Molecular Diagnostics Lab, Nemours Children's Health, Delaware
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Jul 22, 2020)
maternalclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedmaternalyes2not providednot provided2not providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing
(GTR000500853.3)
PubMed (2)
2not provided1not providednot providedclinical testing
(GTR000500853.3)
PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1maternalyes1bloodnot provided
(GTR000500853.3)
1not providednot providednot provided
2maternalyes1bloodnot provided
(GTR000500853.3)
1not providednot providednot provided

Last Updated: Sep 29, 2024