Variant 19-43526151-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014297.5(ETHE1):c.375+50A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00783 in 1,613,460 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 56 hom. )

Consequence

ETHE1
NM_014297.5 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.75

Variant links:

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]

ETHE1 links:

ZNF575 (HGNC:27606): (zinc finger protein 575) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF575 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 19-43526151-T-G is Benign according to our data. Variant chr19-43526151-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1192898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00525 (798/152020) while in subpopulation NFE AF= 0.00836 (568/67968). AF 95% confidence interval is 0.00779. There are 2 homozygotes in gnomad4. There are 384 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETHE1	NM_014297.5 linkuse as main transcript	c.375+50A>C		intron_variant		ENST00000292147.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETHE1	ENST00000292147.7 linkuse as main transcript	c.375+50A>C		intron_variant		1	NM_014297.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00525

AC:

798

AN:

151902

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00584

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00836

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00504

AC:

1260

AN:

250246

Hom.:

AF XY:

0.00507

AC XY:

686

AN XY:

135412

show subpopulations

Gnomad AFR exome

AF:

0.00125

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00363

Gnomad FIN exome

AF:

0.000605

Gnomad NFE exome

AF:

0.00824

Gnomad OTH exome

AF:

0.00491

GnomAD4 exome

AF:

0.00809

AC:

11828

AN:

1461440

Hom.:

Cov.:

AF XY:

0.00795

AC XY:

5781

AN XY:

726984

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00418

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00417

Gnomad4 FIN exome

AF:

0.000901

Gnomad4 NFE exome

AF:

0.00971

Gnomad4 OTH exome

AF:

0.00583

GnomAD4 genome

AF:

0.00525

AC:

798

AN:

152020

Hom.:

Cov.:

AF XY:

0.00517

AC XY:

384

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00181

Gnomad4 AMR

AF:

0.00583

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.00836

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00669

Hom.:

Bravo

AF:

0.00512

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 13, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.4

DANN

Benign

0.76

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over