NM_198437.3:c.91T>A

Variant names:

• chr20-56386485-A-T
• rs2273535
• NM_198437.3:c.91T>A
• AURKA p.Phe31Ile

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+4 Uncertain · Hot

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 4 classification points (ACGS-UK Somatic Oncogenicity v2025). O1_StrongO4_SupportingB3_Supporting

The NM_198437.3(AURKA):c.91T>A (p.Phe31Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The gene AURKA is a tumor suppressor gene (CancerMine: 4 TSG, 51 oncogene, 8 driver citations). The gene AURKA is a known oncogene (CancerMine: 4 TSG, 51 oncogene, 8 driver citations). The gene AURKA is a cancer driver gene (CancerMine: 4 TSG, 51 oncogene, 8 driver citations). The variant allele was found at a cumulative frequency of 0.235 (AC=379,568) in the gnomAD database across 1,613,914 control chromosomes, including 50,544 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.659. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★). This exact variant is established as oncogenic in: CGI (Cancer Genome Interpreter). The variant has been observed in cBioPortal in 13 samples across 5 studies and 9 cancer types; somatic enrichment level: SUPPORTING (Observed repeatedly in cBioPortal somatic datasets.). This exact variant is curated in the UniProt human variants database as Uncertain Significance; it is also listed as a COSMIC curated somatic variant.

• Frequency:
  • Genomes: 𝑓 0.22 (4562 hom., cov: 33)
  • Exomes 𝑓: 0.24 (45982 hom.)
• Consequence: AURKA NM_198437.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: -0.555
• Publications: 114 publications found

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]

AURKA Gene-Disease associations (from GenCC):

• breast cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 4 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O1Established oncogenic variant		CGI exact DNA-change oncogenic — Strong (O1); O1 contributing sources (4.0 pts): CGI (Cancer Genome Interpreter)
	O4Enriched in somatic variant database		Enriched in cBioPortal (pre-computed score ≥ 1.0) — Supporting (O4); cBioPortal: samples=13 | studies=5 | cancer types=9 | level=SUPPORTING | points=1.0 | reason: Observed repeatedly in cBioPortal somatic datasets.
	B3Computational evidence does not support deleterious effect		Computational evidence does not support a deleterious effect; Missense variant — primary computational scorer does not support an oncogenic/deleterious effect; supports B3

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_198437.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	AURKA NM_198437.3	MANE Select	c.91T>A p.Phe31Ile	missense	Exon 3 of 9	Prot: NP_940839.1 UniProt:
	AURKA NM_001424418.1		c.193T>A p.Phe65Ile	missense	Exon 5 of 11	Prot: NP_001411347.1
	AURKA NM_001424419.1		c.193T>A p.Phe65Ile	missense	Exon 5 of 11	Prot: NP_001411348.1

AURKA NM_198437.3

MANE Select

HGVSc / HGVSpc.91T>Ap.Phe31Ile

Exon rankExon 3 of 9

missense

Prot: NP_940839.1UniProt: O14965

AURKA NM_001424418.1

HGVSc / HGVSpc.193T>Ap.Phe65Ile

Exon rankExon 5 of 11

missense

Prot: NP_001411347.1

AURKA NM_001424419.1

HGVSc / HGVSpc.193T>Ap.Phe65Ile

Exon rankExon 5 of 11

missense

Prot: NP_001411348.1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	AURKA ENST00000395915.8	TSL:1MANE Select	c.91T>A p.Phe31Ile	missense	Exon 3 of 9	Prot: ENSP00000379251.3 UniProt:
	AURKA ENST00000312783.10	TSL:1	c.91T>A p.Phe31Ile	missense	Exon 4 of 10	Prot: ENSP00000321591.6 UniProt:
	AURKA ENST00000347343.6	TSL:1	c.91T>A p.Phe31Ile	missense	Exon 3 of 9	Prot: ENSP00000216911.2 UniProt:

AURKA ENST00000395915.8

TSL:1MANE Select

HGVSc / HGVSpc.91T>Ap.Phe31Ile

Exon rankExon 3 of 9

missense

Prot: ENSP00000379251.3UniProt: O14965

AURKA ENST00000312783.10

TSL:1

HGVSc / HGVSpc.91T>Ap.Phe31Ile

Exon rankExon 4 of 10

missense

Prot: ENSP00000321591.6UniProt: O14965

AURKA ENST00000347343.6

TSL:1

HGVSc / HGVSpc.91T>Ap.Phe31Ile

Exon rankExon 3 of 9

missense

Prot: ENSP00000216911.2UniProt: O14965

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.223	AC:33952	Hom:4556	AN:152018	Cov:33
GnomAD2 exomes	AF: 0.278	AC:69789	Hom:	AN:251444	Cov:
GnomAD4 exome	AF: 0.236	AC:345594	Hom:45982	AN:1461776	Cov:41
GnomAD4 genome	AF: 0.223	AC:33974	Hom:4562	AN:152138	Cov:33
TOPMed (Bravo)	AF: 0.222	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.173	AC:8732	Hom:988	AN:50362	Cov:
Local & regional cohorts 11 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.213	AC:498	Hom:49	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.671	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.257	AC:77	Hom:	AN:300	Cov:
ESP6500 (Exome Variant Server)	AF: 0.188	AC:2448	Hom:	AN:13006	Cov:
GenomeAsia100K	AF: 0.453	AC:1576	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.666	AC:4817	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.235	AC:472	Hom:	AN:2010	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.655	AC:80397	Hom:26369	AN:122832	Cov:
Turkish Variome	AF: 0.239	AC:1606	Hom:222	AN:6718	Cov:
UK10K	AF: 0.223	AC:1689	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.690	AC:6181	Hom:2136	AN:8960	Cov:

Showing 17 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
ASC(Autism)	0.231 *	2222	9620	0.233 *	2426	10428
BipEx(Bipolar disorder (including schizoaffective))	0.220	6251	28420	0.218	6281	28844
Epi25(Epilepsy)	0.254	10643	41958	0.234	15626	66884
SCHEMA(Schizophrenia)	0.337	52312	155412	0.313	76764	245496

Showing 4 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	AURKA-related disorder (1)
-	-	-	Colon cancer, susceptibility to (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	12
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.59
DANN	Benign	0.76
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.067	N
FuncVEP CTI	Benign	0.0011
GPN-Star LLR	N/A	-3.7
GPN-Star score	N/A	3.7
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0000035	T
MetaSVM	Benign	-0.99	T
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-0.56
popEVE	Benign	-3.4
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.052
Sift	Benign	0.50	T
Sift4G	Benign	0.40	T
VESM-3B	Benign	-2.0

Showing 25 of 25 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs2273535;

hg19: chr20-54961541;

COSMIC: COSV57167236;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar