21-34799369-G-A
Variant summary
Our verdict is Uncertain significance. Variant got -1 ACMG points: 0P and 1B. BP4
This summary comes from the ClinGen Evidence Repository: NM_001754.5(RUNX1):c.899C>T (p.Thr300Met) is a missense variant. This variant has been seen in gnomADv2.1 at a MAF of 0.00005274 (0.005274%, 6/113766 in the European(non-Finnish) sub-population). This variant does not meet any population criteria. This missense variant has a REVEL score <0.50 (0.423)(BP4). There is no splicing effect predicted (SpliceAI=0). The variant has not been reported in patients with the RUNX1-defined phenotype. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4 LINK:https://erepo.genome.network/evrepo/ui/classification/CA10014273/MONDO:0011071/008
Frequency
Consequence
NM_001754.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.899C>T | p.Thr300Met | missense_variant | 8/9 | ENST00000675419.1 | NP_001745.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RUNX1 | ENST00000675419.1 | c.899C>T | p.Thr300Met | missense_variant | 8/9 | NM_001754.5 | ENSP00000501943 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251492Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135918
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 727246
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74386
ClinVar
Submissions by phenotype
Hereditary thrombocytopenia and hematologic cancer predisposition syndrome Uncertain:1
Uncertain significance, reviewed by expert panel | curation | ClinGen Myeloid Malignancy Variant Curation Expert Panel | Nov 13, 2023 | NM_001754.5(RUNX1):c.899C>T (p.Thr300Met) is a missense variant. This variant has been seen in gnomADv2.1 at a MAF of 0.00005274 (0.005274%, 6/113766 in the European(non-Finnish) sub-population). This variant does not meet any population criteria. This missense variant has a REVEL score <0.50 (0.423)(BP4). There is no splicing effect predicted (SpliceAI=0). The variant has not been reported in patients with the RUNX1-defined phenotype. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4 - |
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 08, 2023 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 300 of the RUNX1 protein (p.Thr300Met). This variant is present in population databases (rs758682659, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 409809). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RUNX1 protein function with a negative predictive value of 80%. 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. - |
Acute myeloid leukemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 26, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at