chr17-36486720-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004773.4(ZNHIT3):c.21C>T(p.Ser7=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,613,928 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.011 ( 31 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 20 hom. )
Consequence
ZNHIT3
NM_004773.4 synonymous
NM_004773.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.821
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
Variant 17-36486720-C-T is Benign according to our data. Variant chr17-36486720-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 784743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0109 (1659/152282) while in subpopulation AFR AF= 0.0368 (1530/41568). AF 95% confidence interval is 0.0353. There are 31 homozygotes in gnomad4. There are 801 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 31 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNHIT3 | NM_004773.4 | c.21C>T | p.Ser7= | synonymous_variant | 1/5 | ENST00000617429.5 | |
LOC105371749 | XR_934710.4 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNHIT3 | ENST00000617429.5 | c.21C>T | p.Ser7= | synonymous_variant | 1/5 | 1 | NM_004773.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0109 AC: 1660AN: 152164Hom.: 31 Cov.: 32
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GnomAD3 exomes AF: 0.00292 AC: 732AN: 251056Hom.: 10 AF XY: 0.00244 AC XY: 331AN XY: 135760
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GnomAD4 exome AF: 0.00107 AC: 1564AN: 1461646Hom.: 20 Cov.: 38 AF XY: 0.000950 AC XY: 691AN XY: 727152
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
ZNHIT3-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 01, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
PEHO syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 27, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at