chrX-154412069-T-C

Variant names:

• chrX-154412069-T-C
• rs62617809
• ENST00000309585.9:c.-351A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000309585.9(DNASE1L1):​c.-351A>G variant causes a 5 prime UTR 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: DNASE1L1 ENST00000309585.9 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267
• Publications: 8 publications found

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]

TAFAZZIN Gene-Disease associations (from GenCC):

• Barth syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAFAZZIN	NM_000116.5	c.110-17T>C		intron_variant	Intron 1 of 10	ENST00000601016.6	NP_000107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAFAZZIN	ENST00000601016.6	c.110-17T>C		intron_variant	Intron 1 of 10	1	NM_000116.5	ENSP00000469981.1

Frequencies

GnomAD3 genomes AF: 0.829 AC: 91819 AN: 110698 Hom.: 27230 Cov.: 23

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

African (AFR) AF: 0.972 AC: 25657 AN: 26386

American (AMR) AF: 0.915 AC: 32092 AN: 35062

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 13073 AN: 19339

East Asian (EAS) AF: 1.00 AC: 30174 AN: 30185

South Asian (SAS) AF: 0.955 AC: 51474 AN: 53904

European-Finnish (FIN) AF: 0.725 AC: 28781 AN: 39697

Middle Eastern (MID) AF: 0.874 AC: 3613 AN: 4135

European-Non Finnish (NFE) AF: 0.745 AC: 626077 AN: 840854

Other (OTH) AF: 0.798 AC: 36700 AN: 45976

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

African (AFR) AF: 0.965 AC: 29484 AN: 30543

American (AMR) AF: 0.874 AC: 9278 AN: 10616

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 1754 AN: 2629

East Asian (EAS) AF: 1.00 AC: 3455 AN: 3455

South Asian (SAS) AF: 0.962 AC: 2506 AN: 2604

European-Finnish (FIN) AF: 0.723 AC: 4276 AN: 5916

Middle Eastern (MID) AF: 0.818 AC: 175 AN: 214

European-Non Finnish (NFE) AF: 0.746 AC: 39214 AN: 52588

Other (OTH) AF: 0.841 AC: 1268 AN: 1508

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
PhyloP100		-0.27
PromoterAI		-0.10	Neutral
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

Other links and lift over

dbSNP: rs62617809; hg19: chrX-153640406;