rs397515742

Variant names:

• chrX-154414088-C-G
• rs397515742
• NM_000116.5:c.371-13C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_000116.5(TAFAZZIN):​c.371-13C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000954 in 1,048,184 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.5e-7 (0 hom. 0 hem.)
• Consequence: TAFAZZIN NM_000116.5 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -0.379
• Publications: 0 publications found

Genes affected

TAFAZZIN (HGNC:11577): (tafazzin, phospholipid-lysophospholipid transacylase) This gene encodes a protein that is expressed at high levels in cardiac and skeletal muscle. Mutations in this gene have been associated with a number of clinical disorders including Barth syndrome, dilated cardiomyopathy (DCM), hypertrophic DCM, endocardial fibroelastosis, and left ventricular noncompaction (LVNC). Multiple transcript variants encoding different isoforms have been described. A long form and a short form of each of these isoforms is produced; the short form lacks a hydrophobic leader sequence and may exist as a cytoplasmic protein rather than being membrane-bound. Other alternatively spliced transcripts have been described but the full-length nature of all these transcripts is not known. [provided by RefSeq, Jul 2008]

TAFAZZIN Gene-Disease associations (from GenCC):

• Barth syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant X-154414088-C-G is Benign according to our data. Variant chrX-154414088-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 42258.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000116.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAFAZZIN	NM_000116.5	MANE Select	c.371-13C>G		intron	N/A	NP_000107.1
	TAFAZZIN	NM_001440856.1		c.425-13C>G		intron	N/A	NP_001427785.1
	TAFAZZIN	NM_001303465.2		c.425-13C>G		intron	N/A	NP_001290394.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAFAZZIN	ENST00000601016.6	TSL:1 MANE Select	c.371-13C>G		intron	N/A	ENSP00000469981.1
	TAFAZZIN	ENST00000475699.6	TSL:1	c.424+521C>G		intron	N/A	ENSP00000419854.3
	TAFAZZIN	ENST00000369776.8	TSL:1	c.295+521C>G		intron	N/A	ENSP00000358791.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.54e-7 AC: 1 AN: 1048184 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 324440

African (AFR) AF: 0.00 AC: 0 AN: 25405

American (AMR) AF: 0.00 AC: 0 AN: 35060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19055

East Asian (EAS) AF: 0.00 AC: 0 AN: 29998

South Asian (SAS) AF: 0.00 AC: 0 AN: 52749

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40447

Middle Eastern (MID) AF: 0.000261 AC: 1 AN: 3838

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 797147

Other (OTH) AF: 0.00 AC: 0 AN: 44485

GnomAD4 genome Cov.: 23

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Dec 09, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The 371-13C>T variant (TAZ) has not been previously reported nor previously iden tified by our laboratory. This variant is located in the 3' splice consensus seq uence, but does not alter the invariant -1/-2 positions. Splicing computational tools do not predict altered splicing, though the accuracy of these tools is unk nown. Additional information is needed to assess the clinical significance of th is variant.

3-Methylglutaconic aciduria type 2 Benign:1

Dec 07, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.65
DANN	Benign	0.81
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs397515742; hg19: chrX-153642425;