rs62617809

Positions:

• chrX-154412069-T-C
• chrX-154412069-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000116.5(TAFAZZIN):​c.110-17T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.83 (27229 hom., 27356 hem., cov: 23)
  • Exomes 𝑓: 0.77 (220394 hom. 281954 hem.)
  • Failed GnomAD Quality Control
• Consequence: TAFAZZIN NM_000116.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267

Genes affected

DNASE1L1 (HGNC:2957): (deoxyribonuclease 1 like 1) This gene encodes a deoxyribonuclease protein that shows high sequence similarity to DNase I. The encoded protein is localized to the endoplasmic reticulum and modified by N-linked glycosylation. Alternate transcriptional splice variants encoding the same protein have been observed. [provided by RefSeq, Jan 2015]

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAFAZZIN	NM_000116.5	c.110-17T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000601016.6	NP_000107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAFAZZIN	ENST00000601016.6	c.110-17T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000116.5	ENSP00000469981

Frequencies

GnomAD3 genomes AF: 0.829 AC: 91819 AN: 110698 Hom.: 27230 Cov.: 23 AF XY: 0.830 AC XY: 27304 AN XY: 32910

Gnomad AFR AF: 0.965

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.963

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.831

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.839

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.774 AC: 847641 AN: 1095538 Hom.: 220394 Cov.: 60 AF XY: 0.780 AC XY: 281954 AN XY: 361522

Gnomad4 AFR exome AF: 0.972

Gnomad4 AMR exome AF: 0.915

Gnomad4 ASJ exome AF: 0.676

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.955

Gnomad4 FIN exome AF: 0.725

Gnomad4 NFE exome AF: 0.745

Gnomad4 OTH exome AF: 0.798

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.830 AC: 91865 AN: 110742 Hom.: 27229 Cov.: 23 AF XY: 0.830 AC XY: 27356 AN XY: 32964

Gnomad4 AFR AF: 0.965

Gnomad4 AMR AF: 0.874

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.962

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.841

Alfa AF: 0.691 Hom.: 5698

Bravo AF: 0.847

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs62617809; hg19: chrX-153640406;