19-57232069-TC-T

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

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, multiple submitters, no conflicts P:4

Conservation

PhyloP100: 6.87
Variant links:
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]

Genome browser will be placed here

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
AURKCNM_001015878.2 linkuse as main transcriptc.145del p.Leu49TrpfsTer23 frameshift_variant 3/7 ENST00000302804.12 NP_001015878.1
AURKCNM_001015879.2 linkuse as main transcriptc.88del p.Leu30TrpfsTer23 frameshift_variant 3/7 NP_001015879.1
AURKCNM_003160.3 linkuse as main transcriptc.43del p.Leu15TrpfsTer23 frameshift_variant 3/7 NP_003151.2
AURKCXM_047439253.1 linkuse as main transcriptc.145del p.Leu49TrpfsTer23 frameshift_variant 3/5 XP_047295209.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AURKCENST00000302804.12 linkuse as main transcriptc.145del p.Leu49TrpfsTer23 frameshift_variant 3/71 NM_001015878.2 ENSP00000302898 A2Q9UQB9-1

Frequencies

GnomAD3 genomes
AF:
0.0000921
AC:
14
AN:
151932
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000459
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000875
AC:
22
AN:
251468
Hom.:
0
AF XY:
0.000110
AC XY:
15
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000231
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000114
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000101
AC:
147
AN:
1461890
Hom.:
1
Cov.:
33
AF XY:
0.000116
AC XY:
84
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000402
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000106
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000921
AC:
14
AN:
152050
Hom.:
0
Cov.:
31
AF XY:
0.0000673
AC XY:
5
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000130
Hom.:
0
Bravo
AF:
0.000106
EpiCase
AF:
0.000164
EpiControl
AF:
0.000296

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 submitterclinical testingEquipe Genetique des Anomalies du Developpement, Université de Bourgogne-- -
Pathogenic, no assertion criteria providedliterature onlyOMIMMay 01, 2007- -
Pathogenic, no assertion criteria providedclinical testingEurofins-BiomnisDec 01, 2022- -
not provided Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Jan 11, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs397515619; hg19: chr19-57743437; API