20-56388190-C-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_198437.3(AURKA):c.8G>T(p.Arg3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,007,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0012 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
AURKA
NM_198437.3 missense
NM_198437.3 missense
Scores
2
14
Clinical Significance
Conservation
PhyloP100: -0.385
Genes affected
AURKA (HGNC:11393): (aurora kinase A) The protein encoded by this gene is a cell cycle-regulated kinase that appears to be involved in microtubule formation and/or stabilization at the spindle pole during chromosome segregation. The encoded protein is found at the centrosome in interphase cells and at the spindle poles in mitosis. This gene may play a role in tumor development and progression. A processed pseudogene of this gene has been found on chromosome 1, and an unprocessed pseudogene has been found on chromosome 10. Multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.006895691).
BS2
?
High AC in GnomAd at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AURKA | NM_198437.3 | c.8G>T | p.Arg3Leu | missense_variant | 2/9 | ENST00000395915.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AURKA | ENST00000395915.8 | c.8G>T | p.Arg3Leu | missense_variant | 2/9 | 1 | NM_198437.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00122 AC: 7AN: 5726Hom.: 0 Cov.: 0
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GnomAD3 exomes AF: 0.0000265 AC: 6AN: 226800Hom.: 0 AF XY: 0.0000323 AC XY: 4AN XY: 123672
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GnomAD4 exome AF: 0.0000110 AC: 11AN: 1001718Hom.: 0 Cov.: 40 AF XY: 0.0000123 AC XY: 6AN XY: 489008
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GnomAD4 genome ? AF: 0.00122 AC: 7AN: 5726Hom.: 0 Cov.: 0 AF XY: 0.00168 AC XY: 5AN XY: 2974
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 07, 2024 | The c.8G>T (p.R3L) alteration is located in exon 4 (coding exon 1) of the AURKA gene. This alteration results from a G to T substitution at nucleotide position 8, causing the arginine (R) at amino acid position 3 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N;N;N;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T;T;T;.;.;.;.;.
Polyphen
0.028, 0.049, 0.12, 0.69, 0.015
.;.;.;.;.;.;.;B;B;B;P;B;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0563);Loss of MoRF binding (P = 0.0563);Loss of MoRF binding (P = 0.0563);Loss of MoRF binding (P = 0.0563);Loss of MoRF binding (P = 0.0563);Loss of MoRF binding (P = 0.0563);Loss of MoRF binding (P = 0.0563);Loss of MoRF binding (P = 0.0563);Loss of MoRF binding (P = 0.0563);Loss of MoRF binding (P = 0.0563);Loss of MoRF binding (P = 0.0563);Loss of MoRF binding (P = 0.0563);Loss of MoRF binding (P = 0.0563);
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
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