rs749123022

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2

The NM_001015878.2(AURKC):​c.94_101delAGCCCAGC​(p.Ser32HisfsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000205 in 1,613,434 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

AURKC
NM_001015878.2 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36
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 Likely_pathogenic. Variant got 6 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.899 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AURKCNM_001015878.2 linkc.94_101delAGCCCAGC p.Ser32HisfsTer8 frameshift_variant Exon 2 of 7 ENST00000302804.12 NP_001015878.1 Q9UQB9-1
AURKCNM_001015879.2 linkc.37_44delAGCCCAGC p.Ser13HisfsTer8 frameshift_variant Exon 2 of 7 NP_001015879.1 Q9UQB9-3
AURKCXM_047439253.1 linkc.94_101delAGCCCAGC p.Ser32HisfsTer8 frameshift_variant Exon 2 of 5 XP_047295209.1
AURKCNM_003160.3 linkc.-9_-2delAGCCCAGC 5_prime_UTR_variant Exon 2 of 7 NP_003151.2 Q9UQB9-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AURKCENST00000302804.12 linkc.94_101delAGCCCAGC p.Ser32HisfsTer8 frameshift_variant Exon 2 of 7 1 NM_001015878.2 ENSP00000302898.6 Q9UQB9-1

Frequencies

GnomAD3 genomes
AF:
0.000139
AC:
21
AN:
151432
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000219
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000132
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000194
Gnomad SAS
AF:
0.000210
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.000482
GnomAD3 exomes
AF:
0.000148
AC:
37
AN:
250472
Hom.:
0
AF XY:
0.000155
AC XY:
21
AN XY:
135450
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.000457
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000142
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000212
AC:
310
AN:
1461884
Hom.:
0
AF XY:
0.000223
AC XY:
162
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000378
Gnomad4 SAS exome
AF:
0.000614
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.000189
Gnomad4 OTH exome
AF:
0.000298
GnomAD4 genome
AF:
0.000139
AC:
21
AN:
151550
Hom.:
0
Cov.:
31
AF XY:
0.000122
AC XY:
9
AN XY:
74016
show subpopulations
Gnomad4 AFR
AF:
0.000218
Gnomad4 AMR
AF:
0.000132
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.000210
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.000477
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.000125
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs749123022; hg19: chr19-57743127; API