chrX-154420024-CT-C

Variant names:

• chrX-154420024-CT-C
• rs782192927
• NM_000116.5:c.584-7delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_000116.5(TAFAZZIN):​c.584-7delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,210,172 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., 5 hem., cov: 23)
  • Exomes 𝑓: 0.000021 (0 hom. 14 hem.)
• Consequence: TAFAZZIN NM_000116.5 splice_region, intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.20
• 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: Benign. The variant received -16 ACMG points.

• BP6: Variant X-154420024-CT-C is Benign according to our data. Variant chrX-154420024-CT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 221026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000142 (16/112340) while in subpopulation AFR AF = 0.000485 (15/30943). AF 95% confidence interval is 0.000298. There are 0 homozygotes in GnomAd4. There are 5 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 5 XL gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAFAZZIN	NM_000116.5	MANE Select	c.584-7delT		splice_region intron	N/A	NP_000107.1
	TAFAZZIN	NM_001440856.1		c.638-7delT		splice_region intron	N/A	NP_001427785.1
	TAFAZZIN	NM_001303465.2		c.596-7delT		splice_region intron	N/A	NP_001290394.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAFAZZIN	ENST00000601016.6	TSL:1 MANE Select	c.584-7delT		splice_region intron	N/A	ENSP00000469981.1
	TAFAZZIN	ENST00000475699.6	TSL:1	c.548-7delT		splice_region intron	N/A	ENSP00000419854.3
	TAFAZZIN	ENST00000369776.8	TSL:1	c.377-7delT		splice_region intron	N/A	ENSP00000358791.4

Frequencies

GnomAD3 genomes AF: 0.000142 AC: 16 AN: 112340 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000664

GnomAD2 exomes AF: 0.0000381 AC: 7 AN: 183500 AF XY: 0.0000736

Gnomad AFR exome AF: 0.000380

Gnomad AMR exome AF: 0.0000729

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000210 AC: 23 AN: 1097832 Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 14 AN XY: 363208

African (AFR) AF: 0.000606 AC: 16 AN: 26395

American (AMR) AF: 0.0000568 AC: 2 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.00 AC: 0 AN: 54141

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4108

European-Non Finnish (NFE) AF: 0.00000356 AC: 3 AN: 841788

Other (OTH) AF: 0.0000434 AC: 2 AN: 46073

GnomAD4 genome AF: 0.000142 AC: 16 AN: 112340 Hom.: 0 Cov.: 23 AF XY: 0.000145 AC XY: 5 AN XY: 34510

African (AFR) AF: 0.000485 AC: 15 AN: 30943

American (AMR) AF: 0.00 AC: 0 AN: 10728

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3555

South Asian (SAS) AF: 0.00 AC: 0 AN: 2718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6237

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53086

Other (OTH) AF: 0.000664 AC: 1 AN: 1507

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000155

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	3-Methylglutaconic aciduria type 2 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.2
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: rs782192927; hg19: chrX-153648363;