rs764262721
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
This summary comes from the ClinGen Evidence Repository: The NM_001114753.3: c.1711C>T variant in ENG is a missense variant predicted to cause substitution of arginine by cysteine at amino acid 571 (p.Arg571Cys). The highest population minor allele frequency in gnomAD v2.1.1 is 0.0004233 (15/35434 alleles) in the Admixed American population. The computational predictor REVEL gives a score of 0.31, which is neither above nor below the thresholds predicting a damaging or benign impact on ENG function. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal dominant hereditary hemorrhagic telangiectasia based on the ACMG/AMP criteria applied, as specified by the ClinGen Hereditary Hemorrhagic Telangiectasia Variant Curation Expert Panel: None (specification version 1.0.0; 1/4/2024). LINK:https://erepo.genome.network/evrepo/ui/classification/CA5252673/MONDO:0008535/136
Frequency
Consequence
NM_001114753.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.1711C>T | p.Arg571Cys | missense_variant | 13/15 | ENST00000373203.9 | |
LOC102723566 | NR_136302.1 | n.1114G>A | non_coding_transcript_exon_variant | 1/6 | |||
ENG | NM_000118.4 | c.1711C>T | p.Arg571Cys | missense_variant | 13/14 | ||
ENG | NM_001278138.2 | c.1165C>T | p.Arg389Cys | missense_variant | 13/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENG | ENST00000373203.9 | c.1711C>T | p.Arg571Cys | missense_variant | 13/15 | 1 | NM_001114753.3 | P2 | |
ENG | ENST00000344849.4 | c.1711C>T | p.Arg571Cys | missense_variant | 13/14 | 1 | A2 | ||
ENST00000439298.5 | n.1114G>A | non_coding_transcript_exon_variant | 1/6 | 2 | |||||
ENG | ENST00000480266.6 | c.1165C>T | p.Arg389Cys | missense_variant | 13/15 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152208Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251344Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135892
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461868Hom.: 0 Cov.: 30 AF XY: 0.0000330 AC XY: 24AN XY: 727236
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74356
ClinVar
Submissions by phenotype
Telangiectasia, hereditary hemorrhagic, type 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 24, 2021 | - - |
Uncertain significance, reviewed by expert panel | curation | ClinGen Hereditary Hemorrhagic Telangiectasia Variant Curation Expert Panel, ClinGen | Mar 15, 2024 | The NM_001114753.3: c.1711C>T variant in ENG is a missense variant predicted to cause substitution of arginine by cysteine at amino acid 571 (p.Arg571Cys). The highest population minor allele frequency in gnomAD v2.1.1 is 0.0004233 (15/35434 alleles) in the Admixed American population. The computational predictor REVEL gives a score of 0.31, which is neither above nor below the thresholds predicting a damaging or benign impact on ENG function. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal dominant hereditary hemorrhagic telangiectasia based on the ACMG/AMP criteria applied, as specified by the ClinGen Hereditary Hemorrhagic Telangiectasia Variant Curation Expert Panel: None (specification version 1.0.0; 1/4/2024). - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 23, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Variant reported in 1 proband with juvenile polyposis - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 17, 2015 | - - |
Hereditary hemorrhagic telangiectasia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at