rs1182227189
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_022051.3(EGLN1):βc.122_124delβ(p.Tyr41del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000193 in 1,555,448 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ).
Frequency
Genomes: π 0.0000066 ( 0 hom., cov: 32)
Exomes π: 0.0000014 ( 0 hom. )
Consequence
EGLN1
NM_022051.3 inframe_deletion
NM_022051.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.48
Genes affected
EGLN1 (HGNC:1232): (egl-9 family hypoxia inducible factor 1) The protein encoded by this gene catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. HIF is a transcriptional complex that plays a central role in mammalian oxygen homeostasis. This protein functions as a cellular oxygen sensor, and under normal oxygen concentration, modification by prolyl hydroxylation is a key regulatory event that targets HIF subunits for proteasomal destruction via the von Hippel-Lindau ubiquitylation complex. Mutations in this gene are associated with erythrocytosis familial type 3 (ECYT3). [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_022051.3. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EGLN1 | NM_022051.3 | c.122_124del | p.Tyr41del | inframe_deletion | 1/5 | ENST00000366641.4 | |
EGLN1 | NM_001377260.1 | c.122_124del | p.Tyr41del | inframe_deletion | 1/4 | ||
EGLN1 | NM_001377261.1 | c.122_124del | p.Tyr41del | inframe_deletion | 1/4 | ||
EGLN1 | XM_024447734.2 | c.122_124del | p.Tyr41del | inframe_deletion | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EGLN1 | ENST00000366641.4 | c.122_124del | p.Tyr41del | inframe_deletion | 1/5 | 1 | NM_022051.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000659 AC: 1AN: 151798Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000142 AC: 2AN: 1403650Hom.: 0 AF XY: 0.00000287 AC XY: 2AN XY: 697030
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GnomAD4 genome ? AF: 0.00000659 AC: 1AN: 151798Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74160
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Erythrocytosis, familial, 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 14, 2017 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. This variant has not been reported in the literature in individuals with EGLN1-related disease. This variant is not present in population databases (ExAC no frequency). This variant, c.122_124delACT, results in the deletion of 1 amino acid of the EGLN1 protein (p.Tyr41del), but otherwise preserves the integrity of the reading frame. - |
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at