Genetic Variant ENST00000600651.5:c.*128G>T (chr19-43507745-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The ENST00000600651.5(ETHE1):c.*128G>T 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 9)

Exomes 𝑓: 0.000017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ETHE1
ENST00000600651.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.402

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

ethylmalonic encephalopathy
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
Leigh syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ETHE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000600651.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ETHE1	NM_014297.5	MANE Select	c.712+199G>T	intron	N/A	NP_055112.2
ETHE1	NM_001320867.2		c.679+199G>T	intron	N/A	NP_001307796.1	A0A0S2Z580
ETHE1	NM_001320869.2		c.418+199G>T	intron	N/A	NP_001307798.1	A0A0S2Z5N8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ETHE1	ENST00000600651.5	TSL:1	c.*128G>T	3_prime_UTR	Exon 6 of 6	ENSP00000469037.1	M0QXB5
ETHE1	ENST00000292147.7	TSL:1 MANE Select	c.712+199G>T	intron	N/A	ENSP00000292147.1	O95571
ETHE1	ENST00000880125.1		c.877+199G>T	intron	N/A	ENSP00000550184.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

68626

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000167

AC:

AN:

239500

Hom.:

Cov.:

AF XY:

0.0000154

AC XY:

AN XY:

130260

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

6618

American (AMR)

AF:

0.00

AC:

AN:

11412

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6454

East Asian (EAS)

AF:

0.00

AC:

AN:

11468

South Asian (SAS)

AF:

0.00

AC:

AN:

37062

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

844

European-Non Finnish (NFE)

AF:

0.0000283

AC:

AN:

141244

Other (OTH)

AF:

0.00

AC:

AN:

12022

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.300

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

68702

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32600

African (AFR)

AF:

0.00

AC:

AN:

16220

American (AMR)

AF:

0.00

AC:

AN:

5818

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1982

East Asian (EAS)

AF:

0.00

AC:

AN:

2084

South Asian (SAS)

AF:

0.00

AC:

AN:

1512

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3750

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

35998

Other (OTH)

AF:

0.00

AC:

AN:

904

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.6

(source)

DANN

Benign

0.78

PhyloP100

-0.40

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over