chr11-125894017-CCTT-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_031307.4(PUS3):c.1211_1213del(p.Glu404del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000867 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
PUS3
NM_031307.4 inframe_deletion
NM_031307.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.42
Genes affected
PUS3 (HGNC:25461): (pseudouridine synthase 3) The protein encoded by this gene catalyzes the formation of tRNA pseudouridine from tRNA uridine at position 39 in the anticodon stem and loop of transfer RNAs. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]
HYLS1 (HGNC:26558): (HYLS1 centriolar and ciliogenesis associated) This gene encodes a protein localized to the cytoplasm. Mutations in this gene are associated with hydrolethalus syndrome. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_031307.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PUS3 | NM_031307.4 | c.1211_1213del | p.Glu404del | inframe_deletion | 4/4 | ENST00000227474.8 | |
HYLS1 | NM_001134793.2 | c.-26+2548_-26+2550del | intron_variant | ENST00000425380.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PUS3 | ENST00000227474.8 | c.1211_1213del | p.Glu404del | inframe_deletion | 4/4 | 1 | NM_031307.4 | P1 | |
HYLS1 | ENST00000425380.7 | c.-26+2548_-26+2550del | intron_variant | 3 | NM_001134793.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152208Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251452Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135902
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461882Hom.: 0 AF XY: 0.00000688 AC XY: 5AN XY: 727244
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74350
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 16, 2022 | The c.1211_1213delAAG (p.E404del) alteration is located in exon 4 (coding exon 3) of the PUS3 gene. This alteration consists of an in-frame deletion of 3 nucleotides between nucleotide positions c.1211 and c.1213, resulting in the deletion of 1 residue. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at