NM_000116.5(TAFAZZIN):c.646+14C>T AND not specified

Germline classification:: Benign (4 submissions)
Last evaluated:: Sep 2, 2019
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:: RCV000155815.8

Allele description [Variation Report for NM_000116.5(TAFAZZIN):c.646+14C>T]

NM_000116.5(TAFAZZIN):c.646+14C>T

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.646+14C>T

HGVS:

NC_000023.11:g.154420108C>T
NG_009634.1:g.13571C>T
NM_000116.5:c.646+14C>TMANE SELECT
NM_001303465.2:c.658+14C>T
NM_181311.4:c.556+14C>T
NM_181312.4:c.604+14C>T
NM_181313.4:c.514+14C>T
LRG_131t1:c.646+14C>T
NC_000023.10:g.153648447C>T
NM_000116.3:c.646+14C>T
NM_000116.4:c.646+14C>T

Links:

dbSNP: rs191527230

NCBI 1000 Genomes Browser:

rs191527230

Molecular consequence:

NM_000116.5:c.646+14C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001303465.2:c.658+14C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_181311.4:c.556+14C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_181312.4:c.604+14C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_181313.4:c.514+14C>T - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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PREDICTED: Rattus norvegicus decapping exoribonuclease (Dxo), transcript variant...
PREDICTED: Rattus norvegicus decapping exoribonuclease (Dxo), transcript variant X1, mRNA
gi|2678924629|ref|XM_039098809.2|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000171954	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Feb 12, 2014)	germline	clinical testing	Citation Link,
SCV000205526	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Benign (Aug 11, 2013)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001362334	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Sep 2, 2019)	germline	clinical testing	Citation Link,
SCV001921085	Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing

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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	not provided	2	2	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From GeneDx, SCV000171954.11

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

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

#	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 Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000205526.5

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

Description

646+14C>T in intron 8 of TAZ: This variant is not expected to have clinical sign ificance because it is not located within the conserved splice consensus sequenc e. It has been identified in 0.8% (32/3835) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washing ton.edu/EVS; dbSNP rs191527230).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		2	not provided	2	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001362334.1

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

Description

Variant summary: TAZ c.646+14C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00064 in 183439 control chromosomes, predominantly at a frequency of 0.0071 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 3.2 fold of the estimated maximal expected allele frequency for a pathogenic variant in TAZ causing Barth Syndrome phenotype (0.0022), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.646+14C>T in individuals affected with Barth Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. However, two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar before 2014 and have settled on a classification as benign. Based on the evidence outlined above, the variant was classified as benign.

#	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 Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001921085.1

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

Last Updated: Sep 29, 2024

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