chr11-125894082-A-G
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_031307.4(PUS3):āc.1149T>Cā(p.Asp383=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,613,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00016 ( 0 hom., cov: 32)
Exomes š: 0.00014 ( 0 hom. )
Consequence
PUS3
NM_031307.4 synonymous
NM_031307.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.656
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 Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 11-125894082-A-G is Benign according to our data. Variant chr11-125894082-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2193909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.656 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PUS3 | NM_031307.4 | c.1149T>C | p.Asp383= | synonymous_variant | 4/4 | ENST00000227474.8 | |
HYLS1 | NM_001134793.2 | c.-26+2610A>G | intron_variant | ENST00000425380.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PUS3 | ENST00000227474.8 | c.1149T>C | p.Asp383= | synonymous_variant | 4/4 | 1 | NM_031307.4 | P1 | |
HYLS1 | ENST00000425380.7 | c.-26+2610A>G | intron_variant | 3 | NM_001134793.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152076Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000596 AC: 15AN: 251468Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135914
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GnomAD4 exome AF: 0.000137 AC: 200AN: 1461880Hom.: 0 Cov.: 33 AF XY: 0.000113 AC XY: 82AN XY: 727244
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GnomAD4 genome AF: 0.000164 AC: 25AN: 152076Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74278
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 14, 2022 | - - |
PUS3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 21, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
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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