rs757570529
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001754.5(RUNX1):c.801G>A(p.Met267Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000851 in 1,609,336 control chromosomes in the GnomAD database, with no homozygous occurrence. 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_001754.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.801G>A | p.Met267Ile | missense_variant | 7/9 | ENST00000675419.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RUNX1 | ENST00000675419.1 | c.801G>A | p.Met267Ile | missense_variant | 7/9 | NM_001754.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151924Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000402 AC: 10AN: 248848Hom.: 0 AF XY: 0.0000446 AC XY: 6AN XY: 134580
GnomAD4 exome AF: 0.0000899 AC: 131AN: 1457412Hom.: 0 Cov.: 32 AF XY: 0.0000870 AC XY: 63AN XY: 723974
GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 151924Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74208
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 | Oct 17, 2023 | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 267 of the RUNX1 protein (p.Met267Ile). This variant is present in population databases (rs757570529, gnomAD 0.007%). This missense change has been observed in individual(s) with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) (PMID: 24523240, 27137476, 34166225). This variant is also known as p.Met240Ile. ClinVar contains an entry for this variant (Variation ID: 409818). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change does not substantially affect RUNX1 function (PMID: 34166225). 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 | Sep 26, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at