rs727503038
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_001114753.3(ENG):c.818C>T(p.Thr273Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T273T) has been classified as Likely benign.
Frequency
Consequence
NM_001114753.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.818C>T | p.Thr273Ile | missense_variant, splice_region_variant | 7/15 | ENST00000373203.9 | |
ENG | NM_000118.4 | c.818C>T | p.Thr273Ile | missense_variant, splice_region_variant | 7/14 | ||
ENG | NM_001278138.2 | c.272C>T | p.Thr91Ile | missense_variant, splice_region_variant | 7/15 | ||
ENG | NM_001406715.1 | c.818C>T | p.Thr273Ile | missense_variant, splice_region_variant | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENG | ENST00000373203.9 | c.818C>T | p.Thr273Ile | missense_variant, splice_region_variant | 7/15 | 1 | NM_001114753.3 | P2 | |
ENG | ENST00000344849.4 | c.818C>T | p.Thr273Ile | missense_variant, splice_region_variant | 7/14 | 1 | A2 | ||
ENG | ENST00000480266.6 | c.272C>T | p.Thr91Ile | missense_variant, splice_region_variant | 7/15 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 28
GnomAD4 exome Cov.: 33
GnomAD4 genome ? Cov.: 28
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 16, 2015 | - - |
Hereditary hemorrhagic telangiectasia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 163407). This missense change has been observed in individual(s) with clinical features of hereditary hemorrhagic telangiectasia (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 273 of the ENG protein (p.Thr273Ile). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at