chr19-57231110-C-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The ENST00000302804.12(AURKC):c.-139C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000316 in 1,529,968 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00034 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00031 ( 1 hom. )
Consequence
AURKC
ENST00000302804.12 5_prime_UTR
ENST00000302804.12 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.05
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 Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000337 (51/151316) while in subpopulation EAS AF= 0.00729 (37/5074). AF 95% confidence interval is 0.00544. There are 0 homozygotes in gnomad4. There are 28 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| AURKC | NM_001015878.2 | c.-139C>T | 5_prime_UTR_variant | 1/7 | ENST00000302804.12 | NP_001015878.1 | ||
| AURKC | NM_001015879.2 | c.-4C>T | 5_prime_UTR_variant | 1/7 | NP_001015879.1 | |||
| AURKC | NM_003160.3 | c.-54C>T | 5_prime_UTR_variant | 1/7 | NP_003151.2 | |||
| AURKC | XM_047439253.1 | c.-139C>T | 5_prime_UTR_variant | 1/5 | XP_047295209.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| AURKC | ENST00000302804.12 | c.-139C>T | 5_prime_UTR_variant | 1/7 | 1 | NM_001015878.2 | ENSP00000302898 | A2 | ||
| AURKC | ENST00000415300.6 | c.-4C>T | 5_prime_UTR_variant | 1/7 | 1 | ENSP00000407162 | ||||
| AURKC | ENST00000601799.5 | upstream_gene_variant | 3 | ENSP00000468918 |
Frequencies
GnomAD3 genomes 0.000337 AC: 51AN: 151196Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000860 AC: 114AN: 132630Hom.: 1 AF XY: 0.000855 AC XY: 60AN XY: 70144
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GnomAD4 exome AF: 0.000314 AC: 433AN: 1378652Hom.: 1 Cov.: 38 AF XY: 0.000338 AC XY: 230AN XY: 680854
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GnomAD4 genome 0.000337 AC: 51AN: 151316Hom.: 0 Cov.: 31 AF XY: 0.000379 AC XY: 28AN XY: 73858
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Infertility associated with multi-tailed spermatozoa and excessive DNA Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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