chrX-154411861-G-A

Variant names:

• chrX-154411861-G-A
• rs782245384
• NM_000116.5:c.18G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000116.5(TAFAZZIN):​c.18G>A​(p.Lys6Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000092 in 1,086,652 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: TAFAZZIN NM_000116.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• 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]

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]

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=-0.6).
• BP7: Synonymous conserved (PhyloP=-0.263 with no splicing effect.

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.18G>A	p.Lys6Lys	synonymous	Exon 1 of 11	NP_000107.1	Q16635-1
	TAFAZZIN	NM_001440856.1		c.18G>A	p.Lys6Lys	synonymous	Exon 1 of 11	NP_001427785.1
	TAFAZZIN	NM_001303465.2		c.18G>A	p.Lys6Lys	synonymous	Exon 1 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.18G>A	p.Lys6Lys	synonymous	Exon 1 of 11	ENSP00000469981.1	Q16635-1
	TAFAZZIN	ENST00000475699.6	TSL:1	c.18G>A	p.Lys6Lys	synonymous	Exon 1 of 10	ENSP00000419854.3	A0A499FJ53
	TAFAZZIN	ENST00000369776.8	TSL:1	c.18G>A	p.Lys6Lys	synonymous	Exon 1 of 7	ENSP00000358791.4	F6Y2X3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.20e-7 AC: 1 AN: 1086652 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 356980

African (AFR) AF: 0.00 AC: 0 AN: 26315

American (AMR) AF: 0.00 AC: 0 AN: 34533

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19192

East Asian (EAS) AF: 0.00 AC: 0 AN: 29920

South Asian (SAS) AF: 0.00 AC: 0 AN: 53121

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34933

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3963

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 838995

Other (OTH) AF: 0.00 AC: 0 AN: 45680

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.2
DANN	Benign	0.97
PhyloP100		-0.26
PromoterAI		0.34	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs782245384; hg19: chrX-153640198; COSMIC: COSV50010068; COSMIC: COSV50010068;