rs2599450

Variant names:

• chr19-43507745-C-A
• rs2599450
• ENST00000600651.5:c.*128G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-43507745-C-A
• chr19-43507745-C-G
• chr19-43507745-C-T

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402
• Publications: 0 publications found

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

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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: 0 AN: 68626 Hom.: 0 Cov.: 9

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: 4 AN: 239500 Hom.: 0 Cov.: 2 AF XY: 0.0000154 AC XY: 2 AN XY: 130260

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

African (AFR) AF: 0.00 AC: 0 AN: 6618

American (AMR) AF: 0.00 AC: 0 AN: 11412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6454

East Asian (EAS) AF: 0.00 AC: 0 AN: 11468

South Asian (SAS) AF: 0.00 AC: 0 AN: 37062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 844

European-Non Finnish (NFE) AF: 0.0000283 AC: 4 AN: 141244

Other (OTH) AF: 0.00 AC: 0 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.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 68702 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 32600

African (AFR) AF: 0.00 AC: 0 AN: 16220

American (AMR) AF: 0.00 AC: 0 AN: 5818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1982

East Asian (EAS) AF: 0.00 AC: 0 AN: 2084

South Asian (SAS) AF: 0.00 AC: 0 AN: 1512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3750

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 98

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 35998

Other (OTH) AF: 0.00 AC: 0 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
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

Other links and lift over

dbSNP: rs2599450; hg19: chr19-44011897;