chrX-154420108-C-T

Variant names:

• chrX-154420108-C-T
• rs191527230
• ENST00000369776.8:c.453C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The ENST00000369776.8(TAFAZZIN):​c.453C>T​(p.Asp151Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000355 in 1,209,512 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 101 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 0.0019 (0 hom., 50 hem., cov: 23)
  • Exomes 𝑓: 0.00020 (0 hom. 51 hem.)
• Consequence: TAFAZZIN ENST00000369776.8 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -2.19
• 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, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant X-154420108-C-T is Benign according to our data. Variant chrX-154420108-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 139390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.19 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00188 (211/112023) while in subpopulation AFR AF = 0.00658 (203/30874). AF 95% confidence interval is 0.00583. There are 0 homozygotes in GnomAd4. There are 50 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 50 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369776.8. 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.646+14C>T		intron	N/A	NP_000107.1	Q16635-1
	TAFAZZIN	NM_001440856.1		c.700+14C>T		intron	N/A	NP_001427785.1
	TAFAZZIN	NM_001303465.2		c.658+14C>T		intron	N/A	NP_001290394.1	A6XNE1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAFAZZIN	ENST00000369776.8	TSL:1	c.453C>T	p.Asp151Asp	synonymous	Exon 5 of 7	ENSP00000358791.4	F6Y2X3
	TAFAZZIN	ENST00000601016.6	TSL:1 MANE Select	c.646+14C>T		intron	N/A	ENSP00000469981.1	Q16635-1
	TAFAZZIN	ENST00000475699.6	TSL:1	c.610+14C>T		intron	N/A	ENSP00000419854.3	A0A499FJ53

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 211 AN: 111968 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00659

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000564

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000377

Gnomad OTH AF: 0.000664

GnomAD2 exomes AF: 0.000643 AC: 118 AN: 183439 AF XY: 0.000339

Gnomad AFR exome AF: 0.00707

Gnomad AMR exome AF: 0.000401

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000721

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000244

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.000199 AC: 218 AN: 1097489 Hom.: 0 Cov.: 31 AF XY: 0.000141 AC XY: 51 AN XY: 362879

African (AFR) AF: 0.00614 AC: 162 AN: 26387

American (AMR) AF: 0.000398 AC: 14 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19381

East Asian (EAS) AF: 0.000364 AC: 11 AN: 30203

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54137

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4135

European-Non Finnish (NFE) AF: 0.0000154 AC: 13 AN: 841437

Other (OTH) AF: 0.000347 AC: 16 AN: 46072

GnomAD4 genome AF: 0.00188 AC: 211 AN: 112023 Hom.: 0 Cov.: 23 AF XY: 0.00146 AC XY: 50 AN XY: 34257

African (AFR) AF: 0.00658 AC: 203 AN: 30874

American (AMR) AF: 0.000281 AC: 3 AN: 10667

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.000565 AC: 2 AN: 3538

South Asian (SAS) AF: 0.00 AC: 0 AN: 2692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6183

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000377 AC: 2 AN: 52993

Other (OTH) AF: 0.000656 AC: 1 AN: 1524

Alfa AF: 0.000214 Hom.: 1

Bravo AF: 0.00212

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	3-Methylglutaconic aciduria type 2 (2)
-	-	1	Endocardial fibroelastosis (1)
-	-	1	not provided (1)
-	-	1	Primary dilated cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.033
DANN	Benign	0.19
PhyloP100		-2.2
PromoterAI		-0.0062	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs191527230; hg19: chrX-153648447;