rs1554810373
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_001114753.3(ENG):c.673C>T(p.Pro225Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001114753.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.673C>T | p.Pro225Ser | missense_variant | 5/15 | ENST00000373203.9 | NP_001108225.1 | |
ENG | NM_000118.4 | c.673C>T | p.Pro225Ser | missense_variant | 5/14 | NP_000109.1 | ||
ENG | NM_001278138.2 | c.127C>T | p.Pro43Ser | missense_variant | 5/15 | NP_001265067.1 | ||
ENG | NM_001406715.1 | c.673C>T | p.Pro225Ser | missense_variant | 5/8 | NP_001393644.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ENG | ENST00000373203.9 | c.673C>T | p.Pro225Ser | missense_variant | 5/15 | 1 | NM_001114753.3 | ENSP00000362299.4 | ||
ENG | ENST00000344849.4 | c.673C>T | p.Pro225Ser | missense_variant | 5/14 | 1 | ENSP00000341917.3 | |||
ENG | ENST00000480266.6 | c.127C>T | p.Pro43Ser | missense_variant | 5/15 | 2 | ENSP00000479015.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1435834Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 712304
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Telangiectasia, hereditary hemorrhagic, type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Molecular Genetics, Royal Melbourne Hospital | Mar 30, 2023 | This sequence change is predicted to replace proline with serine at codon 225 of the ENG protein (p.(Pro225Ser)). The proline residue is moderately conserved with serine present in two mammals (100 vertebrates, UCSC), and is located in the C-terminal part of the OR1 domain. There is a moderate physicochemical difference between proline and serine. The variant is absent in a large population cohort (gnomAD v2.1 and v3.1), and has not been reported in the relevant medical literature or databases. Multiple lines of computational evidence predict a benign effect for the missense substitution (6/6 algorithms). Based on the classification scheme RMH Modified ACMG Guidelines v1.4.0, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM2_Supporting, BP4. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.