21-34792598-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001754.5(RUNX1):āc.980T>Gā(p.Leu327Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,592,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L327V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001754.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.980T>G | p.Leu327Arg | missense_variant | 9/9 | ENST00000675419.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RUNX1 | ENST00000675419.1 | c.980T>G | p.Leu327Arg | missense_variant | 9/9 | NM_001754.5 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151898Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000497 AC: 1AN: 201184Hom.: 0 AF XY: 0.00000914 AC XY: 1AN XY: 109420
GnomAD4 exome AF: 6.94e-7 AC: 1AN: 1441052Hom.: 0 Cov.: 35 AF XY: 0.00000140 AC XY: 1AN XY: 714938
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151898Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74194
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 06, 2023 | The c.980T>G (p.L327R) alteration is located in exon 9 (coding exon 8) of the RUNX1 gene. This alteration results from a T to G substitution at nucleotide position 980, causing the leucine (L) at amino acid position 327 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 18, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 327 of the RUNX1 protein (p.Leu327Arg). This variant is present in population databases (no rsID available, gnomAD 0.001%). 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: 532654). 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. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at