6-104730377-A-AC
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The NM_020771.4(HACE1):c.2552dupG(p.Gly852TrpfsTer33) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,597,068 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_020771.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152118Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251290Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135808
GnomAD4 exome AF: 0.0000180 AC: 26AN: 1444950Hom.: 0 Cov.: 26 AF XY: 0.0000194 AC XY: 14AN XY: 720132
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152118Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74298
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
PVS1, PM2 -
This sequence change creates a premature translational stop signal (p.Gly852Trpfs*33) in the HACE1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 58 amino acid(s) of the HACE1 protein. This variant is present in population databases (rs745394044, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with HACE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1331677). 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