rs727504330

Variant names:

• chrX-154411827-C-T
• rs727504330
• NM_000116.5:c.-17C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000116.5(TAFAZZIN):​c.-17C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000379 in 1,055,759 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000038 (0 hom. 1 hem.)
• Consequence: TAFAZZIN NM_000116.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.13
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-154411827-C-T is Benign according to our data. Variant chrX-154411827-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 177806.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAFAZZIN	NM_000116.5	MANE Select	c.-17C>T		5_prime_UTR	Exon 1 of 11	NP_000107.1
	TAFAZZIN	NR_024048.3		n.289C>T		non_coding_transcript_exon	Exon 1 of 10
	TAFAZZIN	NM_001440856.1		c.-17C>T		5_prime_UTR	Exon 1 of 11	NP_001427785.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAFAZZIN	ENST00000601016.6	TSL:1 MANE Select	c.-17C>T		5_prime_UTR	Exon 1 of 11	ENSP00000469981.1
	TAFAZZIN	ENST00000475699.6	TSL:1	c.-17C>T		5_prime_UTR	Exon 1 of 10	ENSP00000419854.3
	TAFAZZIN	ENST00000369776.8	TSL:1	c.-17C>T		5_prime_UTR	Exon 1 of 7	ENSP00000358791.4

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000379 AC: 4 AN: 1055759 Hom.: 0 Cov.: 29 AF XY: 0.00000292 AC XY: 1 AN XY: 342789

African (AFR) AF: 0.00 AC: 0 AN: 25548

American (AMR) AF: 0.00 AC: 0 AN: 30049

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18687

East Asian (EAS) AF: 0.00 AC: 0 AN: 28540

South Asian (SAS) AF: 0.00 AC: 0 AN: 51141

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28982

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3431

European-Non Finnish (NFE) AF: 0.00000485 AC: 4 AN: 824743

Other (OTH) AF: 0.00 AC: 0 AN: 44638

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.94
PhyloP100		-1.1
PromoterAI		-0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs727504330; hg19: chrX-153640164;