19-43507745-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000600651.5(ETHE1):c.*128G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (5861 hom., cov: 9)
  • Exomes 𝑓: 0.36 (24629 hom.)
• Consequence: ETHE1 ENST00000600651.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.402

Genes affected

ETHE1 (HGNC:23287): (ETHE1 persulfide dioxygenase) This gene encodes a member of the metallo beta-lactamase family of iron-containing proteins involved in the mitochondrial sulfide oxidation pathway. The encoded protein catalyzes the oxidation of a persulfide substrate to sulfite. Certain mutations in this gene cause ethylmalonic encephalopathy, an infantile metabolic disorder affecting the brain, gastrointestinal tract and peripheral vessels. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 19-43507745-C-T is Benign according to our data. Variant chr19-43507745-C-T is described in ClinVar as [Benign]. Clinvar id is 1260599.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETHE1	NM_014297.5	c.712+199G>A		intron_variant		ENST00000292147.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETHE1	ENST00000600651.5	c.*128G>A		3_prime_UTR_variant	6/6	1
ETHE1	ENST00000292147.7	c.712+199G>A		intron_variant		1	NM_014297.5	P1
ETHE1	ENST00000594342.5	c.*275+199G>A		intron_variant, NMD_transcript_variant		2
ETHE1	ENST00000598330.1	c.*474G>A		3_prime_UTR_variant, NMD_transcript_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.322 AC: 22053 AN: 68430 Hom.: 5853 Cov.: 9

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.357 AC: 85308 AN: 239186 Hom.: 24629 Cov.: 2 AF XY: 0.371 AC XY: 48216 AN XY: 130082

Gnomad4 AFR exome AF: 0.348

Gnomad4 AMR exome AF: 0.528

Gnomad4 ASJ exome AF: 0.256

Gnomad4 EAS exome AF: 0.433

Gnomad4 SAS exome AF: 0.554

Gnomad4 FIN exome AF: 0.277

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.324

GnomAD4 genome AF: 0.322 AC: 22073 AN: 68506 Hom.: 5861 Cov.: 9 AF XY: 0.323 AC XY: 10493 AN XY: 32502

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.318

Alfa AF: 0.421 Hom.: 742

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.3
Dann	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs2599450; hg19: chr19-44011897;