17-36493973-GAC-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004773.4(ZNHIT3):βc.255_256delβ(p.Asp85GlufsTer68) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000186 in 1,613,370 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ).
Frequency
Genomes: π 0.0000066 ( 0 hom., cov: 33)
Exomes π: 0.0000014 ( 0 hom. )
Consequence
ZNHIT3
NM_004773.4 frameshift
NM_004773.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.17
Genes affected
ZNHIT3 (HGNC:12309): (zinc finger HIT-type containing 3) Predicted to enable thyroid hormone receptor binding activity. Predicted to be involved in box C/D snoRNP assembly; maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA); and snoRNA localization. Located in cytoplasm and nucleus. Implicated in PEHO syndrome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNHIT3 | NM_004773.4 | c.255_256del | p.Asp85GlufsTer68 | frameshift_variant | 4/5 | ENST00000617429.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNHIT3 | ENST00000617429.5 | c.255_256del | p.Asp85GlufsTer68 | frameshift_variant | 4/5 | 1 | NM_004773.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251366Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135854
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461212Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726948
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74332
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jun 03, 2024 | Variant summary: ZNHIT3 c.255_256delCA (p.Asp85GlufsX68) results in a premature termination codon in the pentultimate exon, predicted to cause a truncation of the encoded protein, however, nonsense mediated decay is not expected to occur. The variant allele was found at a frequency of 4e-06 in 251366 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.255_256delCA in individuals affected with PEHO Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at