rs1472137141
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_001114753.3(ENG):c.217A>G(p.Thr73Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T73M) has been classified as Likely benign.
Frequency
Consequence
NM_001114753.3 missense, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.217A>G | p.Thr73Ala | missense_variant, splice_region_variant | 2/15 | ENST00000373203.9 | |
ENG | NM_000118.4 | c.217A>G | p.Thr73Ala | missense_variant, splice_region_variant | 2/14 | ||
ENG | NM_001406715.1 | c.217A>G | p.Thr73Ala | missense_variant, splice_region_variant | 2/8 | ||
ENG | NM_001278138.2 | c.-330A>G | splice_region_variant, 5_prime_UTR_variant | 2/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENG | ENST00000373203.9 | c.217A>G | p.Thr73Ala | missense_variant, splice_region_variant | 2/15 | 1 | NM_001114753.3 | P2 | |
ENG | ENST00000344849.4 | c.217A>G | p.Thr73Ala | missense_variant, splice_region_variant | 2/14 | 1 | A2 | ||
ENG | ENST00000480266.6 | c.-330A>G | splice_region_variant, 5_prime_UTR_variant | 2/15 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251284Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135836
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461712Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727166
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Hereditary hemorrhagic telangiectasia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 05, 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 528050). This variant has not been reported in the literature in individuals affected with ENG-related conditions. This variant is present in population databases (rs545936016, gnomAD 0.006%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 73 of the ENG protein (p.Thr73Ala). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at