chr17-36495236-A-AT
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004773.4(ZNHIT3):c.302dupT(p.Leu101PhefsTer53) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,192 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004773.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZNHIT3 | NM_004773.4 | c.302dupT | p.Leu101PhefsTer53 | frameshift_variant | Exon 5 of 5 | ENST00000617429.5 | NP_004764.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000456 AC: 1AN: 219388Hom.: 0 AF XY: 0.00000836 AC XY: 1AN XY: 119546
GnomAD4 exome Cov.: 31
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: ZNHIT3 c.302dupT (p.Leu101PhefsX53) results in a premature termination codon, predicted to cause a truncation of the encoded protein at codon 154. Of note, the encoded protein consists of only 155 amino acids. The variant allele was found at a frequency of 4.6e-06 in 219388 control chromosomes (gnomAD). To our knowledge, no occurrence of c.302dupT in individuals affected with PEHO Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above and given the very close proximity of the premature termination codon to the native termination codon of the protein, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at