rs1554810507
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000373203.9(ENG):c.396_397delinsAA(p.Val133Ile) variant causes a missense 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
ENG
ENST00000373203.9 missense
ENST00000373203.9 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.162
Genes affected
ENG (HGNC:3349): (endoglin) This gene encodes a homodimeric transmembrane protein which is a major glycoprotein of the vascular endothelium. This protein is a component of the transforming growth factor beta receptor complex and it binds to the beta1 and beta3 peptides with high affinity. Mutations in this gene cause hereditary hemorrhagic telangiectasia, also known as Osler-Rendu-Weber syndrome 1, an autosomal dominant multisystemic vascular dysplasia. This gene may also be involved in preeclampsia and several types of cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.396_397delinsAA | p.Val133Ile | missense_variant | 4/15 | ENST00000373203.9 | NP_001108225.1 | |
ENG | NM_000118.4 | c.396_397delinsAA | p.Val133Ile | missense_variant | 4/14 | NP_000109.1 | ||
ENG | NM_001406715.1 | c.396_397delinsAA | p.Val133Ile | missense_variant | 4/8 | NP_001393644.1 | ||
ENG | NM_001278138.2 | c.-151_-150delinsAA | 5_prime_UTR_variant | 4/15 | NP_001265067.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ENG | ENST00000373203.9 | c.396_397delinsAA | p.Val133Ile | missense_variant | 4/15 | 1 | NM_001114753.3 | ENSP00000362299 | P2 | |
ENG | ENST00000344849.4 | c.396_397delinsAA | p.Val133Ile | missense_variant | 4/14 | 1 | ENSP00000341917 | A2 | ||
ENG | ENST00000480266.6 | c.-151_-150delinsAA | 5_prime_UTR_variant | 4/15 | 2 | ENSP00000479015 | ||||
ENG | ENST00000462196.1 | n.296_297delinsAA | non_coding_transcript_exon_variant | 3/4 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary hemorrhagic telangiectasia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 26, 2017 | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an ENG-related disease. This sequence change replaces valine with isoleucine at codon 133 of the ENG protein (p.Val133Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at