rs1157495777
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_001754.5(RUNX1):c.219C>G(p.Ser73Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. S73G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001754.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.219C>G | p.Ser73Arg | missense_variant | 4/9 | ENST00000675419.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RUNX1 | ENST00000675419.1 | c.219C>G | p.Ser73Arg | missense_variant | 4/9 | NM_001754.5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1457112Hom.: 0 Cov.: 35 AF XY: 0.00000276 AC XY: 2AN XY: 724980
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 03, 2020 | 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RUNX1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with arginine at codon 73 of the RUNX1 protein (p.Ser73Arg). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and arginine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at