NM_000116.5:c.657C>T

Variant names:

• chrX-154420222-C-T
• rs140751478
• NM_000116.5:c.657C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_000116.5(TAFAZZIN):​c.657C>T​(p.Asp219Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,209,808 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., 4 hem., cov: 23)
  • Exomes 𝑓: 0.000011 (0 hom. 3 hem.)
• Consequence: TAFAZZIN NM_000116.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.943
• Publications: 2 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, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant X-154420222-C-T is Benign according to our data. Variant chrX-154420222-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 177789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.943 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 4 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.657C>T	p.Asp219Asp	synonymous	Exon 9 of 11	NP_000107.1	Q16635-1
	TAFAZZIN	NM_001440856.1		c.711C>T	p.Asp237Asp	synonymous	Exon 9 of 11	NP_001427785.1
	TAFAZZIN	NM_001303465.2		c.669C>T	p.Asp223Asp	synonymous	Exon 8 of 10	NP_001290394.1	A6XNE1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAFAZZIN	ENST00000601016.6	TSL:1 MANE Select	c.657C>T	p.Asp219Asp	synonymous	Exon 9 of 11	ENSP00000469981.1	Q16635-1
	TAFAZZIN	ENST00000475699.6	TSL:1	c.621C>T	p.Asp207Asp	synonymous	Exon 8 of 10	ENSP00000419854.3	A0A499FJ53
	TAFAZZIN	ENST00000369776.8	TSL:1	c.567C>T	p.Asp189Asp	synonymous	Exon 5 of 7	ENSP00000358791.4	F6Y2X3

Frequencies

GnomAD3 genomes AF: 0.0000807 AC: 9 AN: 111548 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000261

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: 0.0000189

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000545 AC: 10 AN: 183457 AF XY: 0.0000295

Gnomad AFR exome AF: 0.000608

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000244

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 12 AN: 1098207 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 3 AN XY: 363565

African (AFR) AF: 0.000265 AC: 7 AN: 26403

American (AMR) AF: 0.00 AC: 0 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54147

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00000594 AC: 5 AN: 842106

Other (OTH) AF: 0.00 AC: 0 AN: 46097

GnomAD4 genome AF: 0.0000986 AC: 11 AN: 111601 Hom.: 0 Cov.: 23 AF XY: 0.000118 AC XY: 4 AN XY: 33799

African (AFR) AF: 0.000325 AC: 10 AN: 30730

American (AMR) AF: 0.00 AC: 0 AN: 10615

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2638

East Asian (EAS) AF: 0.00 AC: 0 AN: 3545

South Asian (SAS) AF: 0.00 AC: 0 AN: 2631

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52925

Other (OTH) AF: 0.00 AC: 0 AN: 1516

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000121

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	3-Methylglutaconic aciduria type 2 (1)
-	-	1	Cardiovascular phenotype (1)
-	-	1	not provided (1)
-	-	1	TAFAZZIN-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	1.0
DANN	Benign	0.68
PhyloP100		-0.94
PromoterAI		-0.27	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs140751478; hg19: chrX-153648561; COSMIC: COSV54797276; COSMIC: COSV54797276;