rs140790665
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_000601.6(HGF):c.2179C>T(p.Gln727*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000627 in 1,609,760 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000601.6 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000462 AC: 7AN: 151674Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000600 AC: 15AN: 250120Hom.: 0 AF XY: 0.0000666 AC XY: 9AN XY: 135208
GnomAD4 exome AF: 0.0000645 AC: 94AN: 1458086Hom.: 0 Cov.: 30 AF XY: 0.0000551 AC XY: 40AN XY: 725468
GnomAD4 genome AF: 0.0000462 AC: 7AN: 151674Hom.: 0 Cov.: 32 AF XY: 0.0000540 AC XY: 4AN XY: 74078
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change creates a premature translational stop signal (p.Gln727*) in the HGF gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2 amino acid(s) of the HGF protein. This variant is present in population databases (rs140790665, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with HGF-related conditions. ClinVar contains an entry for this variant (Variation ID: 504595). 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. -
not specified Benign:1
p.Gln727X in exon 18 of HGF: This variant is not expected to have clinical signi ficance due to a lack of conservation across species, including mammals. Of note , 4 mammals (lesser Egyptian jerboa, prairie vole, mouse, and rat) have a termin ation codon at or before this position. This alteration occurs within the last e xon and is more likely to escape nonsense mediated decay (NMD) and result in a t runcated protein two amino acids shorter. The variant has also been identified i n 11/125782 European chromosomes by the Genome Aggregation Database (gnomAD, htt p://gnomad.broadinstitute.org/; dbSNP rs140790665). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at