19-57232069-TC-T
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Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The ENST00000302804.12(AURKC):c.145del(p.Leu49TrpfsTer23) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000998 in 1,613,940 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00010 ( 1 hom. )
Consequence
AURKC
ENST00000302804.12 frameshift
ENST00000302804.12 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.87
Genes affected
AURKC (HGNC:11391): (aurora kinase C) This gene encodes a member of the Aurora subfamily of serine/threonine protein kinases. The encoded protein is a chromosomal passenger protein that forms complexes with Aurora-B and inner centromere proteins and may play a role in organizing microtubules in relation to centrosome/spindle function during mitosis. This gene is overexpressed in several cancer cell lines, suggesting an involvement in oncogenic signal transduction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-57232069-TC-T is Pathogenic according to our data. Variant chr19-57232069-TC-T is described in ClinVar as [Pathogenic]. Clinvar id is 6306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-57232069-TC-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AURKC | NM_001015878.2 | c.145del | p.Leu49TrpfsTer23 | frameshift_variant | 3/7 | ENST00000302804.12 | NP_001015878.1 | |
AURKC | NM_001015879.2 | c.88del | p.Leu30TrpfsTer23 | frameshift_variant | 3/7 | NP_001015879.1 | ||
AURKC | NM_003160.3 | c.43del | p.Leu15TrpfsTer23 | frameshift_variant | 3/7 | NP_003151.2 | ||
AURKC | XM_047439253.1 | c.145del | p.Leu49TrpfsTer23 | frameshift_variant | 3/5 | XP_047295209.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AURKC | ENST00000302804.12 | c.145del | p.Leu49TrpfsTer23 | frameshift_variant | 3/7 | 1 | NM_001015878.2 | ENSP00000302898 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000921 AC: 14AN: 151932Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251468Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135916
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GnomAD4 exome AF: 0.000101 AC: 147AN: 1461890Hom.: 1 Cov.: 33 AF XY: 0.000116 AC XY: 84AN XY: 727248
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GnomAD4 genome AF: 0.0000921 AC: 14AN: 152050Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5AN XY: 74328
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Infertility associated with multi-tailed spermatozoa and excessive DNA Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2007 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Eurofins-Biomnis | Dec 01, 2022 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 11, 2016 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at