20-56386483-AAA-GAC

Variant names:

• chr20-56386483-AAA-GAC
• NM_198437.3:c.91_93delTTTinsGTC
• AURKA p.Phe31Val

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_198437.3(AURKA):c.91_93delTTTinsGTC (p.Phe31Val) variant causes a missense change. 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). Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.F31I: Benign (ClinVar VariationId 6642, 2 stars)

• Frequency: Genomes: not found (cov: 33)
• Consequence: AURKA NM_198437.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.956
• Publications: 0 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 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])

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.91_93delTTTinsGTC p.Phe31Val	missense	N/A	Prot: NP_940839.1 UniProt:
	AURKA NM_001424418.1		c.193_195delTTTinsGTC p.Phe65Val	missense	N/A	Prot: NP_001411347.1
	AURKA NM_001424419.1		c.193_195delTTTinsGTC p.Phe65Val	missense	N/A	Prot: NP_001411348.1

AURKA NM_198437.3

MANE Select

HGVSc / HGVSpc.91_93delTTTinsGTCp.Phe31Val

Exon rankN/A

missense

Prot: NP_940839.1UniProt: O14965

AURKA NM_001424418.1

HGVSc / HGVSpc.193_195delTTTinsGTCp.Phe65Val

Exon rankN/A

missense

Prot: NP_001411347.1

AURKA NM_001424419.1

HGVSc / HGVSpc.193_195delTTTinsGTCp.Phe65Val

Exon rankN/A

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.91_93delTTTinsGTC p.Phe31Val	missense	N/A	Prot: ENSP00000379251.3 UniProt:
	AURKA ENST00000312783.10	TSL:1	c.91_93delTTTinsGTC p.Phe31Val	missense	N/A	Prot: ENSP00000321591.6 UniProt:
	AURKA ENST00000347343.6	TSL:1	c.91_93delTTTinsGTC p.Phe31Val	missense	N/A	Prot: ENSP00000216911.2 UniProt:

AURKA ENST00000395915.8

TSL:1MANE Select

HGVSc / HGVSpc.91_93delTTTinsGTCp.Phe31Val

Exon rankN/A

missense

Prot: ENSP00000379251.3UniProt: O14965

AURKA ENST00000312783.10

TSL:1

HGVSc / HGVSpc.91_93delTTTinsGTCp.Phe31Val

Exon rankN/A

missense

Prot: ENSP00000321591.6UniProt: O14965

AURKA ENST00000347343.6

TSL:1

HGVSc / HGVSpc.91_93delTTTinsGTCp.Phe31Val

Exon rankN/A

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 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:33
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:33

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Benign	0.96

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

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

hg19: chr20-54961539;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar