rs1211555765

Variant names:

• chr19-43527255-AGGGCG-A
• rs1211555765
• ENST00000880121.1:c.-83_-79delCGCCC

Your query was ambiguous. Multiple possible variants found:

• chr19-43527255-AGGGCG-A
• chr19-43527255-AGGGCG-AGGGCGGGGCG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000880121.1(ETHE1):​c.-83_-79delCGCCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ETHE1 ENST00000880121.1 5_prime_UTR
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 2.11
• 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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000880121.1. 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.-83_-79delCGCCC		upstream_gene	N/A	NP_055112.2
	ETHE1	NM_001320867.2		c.-83_-79delCGCCC		upstream_gene	N/A	NP_001307796.1	A0A0S2Z580
	ETHE1	NM_001320869.2		c.-83_-79delCGCCC		upstream_gene	N/A	NP_001307798.1	A0A0S2Z5N8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETHE1	ENST00000880121.1		c.-83_-79delCGCCC		5_prime_UTR	Exon 1 of 7	ENSP00000550180.1
	ZNF575	ENST00000458714.2	TSL:2	c.135+630_135+634delGGGCG		intron	N/A	ENSP00000413956.2	B3KQ07
	ZNF575	ENST00000880316.1		c.-195+630_-195+634delGGGCG		intron	N/A	ENSP00000550375.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000150 AC: 2 AN: 1337712 Hom.: 0 AF XY: 0.00000305 AC XY: 2 AN XY: 656078

African (AFR) AF: 0.00 AC: 0 AN: 29644

American (AMR) AF: 0.00 AC: 0 AN: 28548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22174

East Asian (EAS) AF: 0.00 AC: 0 AN: 35056

South Asian (SAS) AF: 0.00 AC: 0 AN: 72826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3838

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1058024

Other (OTH) AF: 0.00 AC: 0 AN: 55572

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	Ethylmalonic encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=34/66	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1211555765; hg19: chr19-44031407;