AURKA p.Phe31Val

Variant names:

• chr20-56386485-A-C
• rs2273535
• NM_198437.3:c.91T>G
• AURKA p.Phe31Val

Your query was ambiguous. Multiple possible variants found:

• chr20-56386485-A-C
• chr20-56386483-AAA-CAC
• chr20-56386483-AAA-GAC
• chr20-56386483-AAA-TAC

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-5 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -5 classification points (ACMG Germline Pathogenicity v2019). PM2_SupportingBS2BP4_Moderate

The NM_198437.3(AURKA):c.91T>G (p.Phe31Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.0000062 (AC=10) in the gnomAD database across 1,613,946 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.0000147. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. 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: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: AURKA NM_198437.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -5 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Rare in gnomAD for AD/XL gene (popmax AF below threshold) — PM2 Supporting; GnomAD popmax AF = 0.0000147 — borderline rare for AD/XL gene (threshold 0.0001) — PM2 supporting.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Moderate).
	BS2Observed in healthy adult		Pure AD gene with cumulative gnomAD AC ≥5 — observed in healthy adults (BS2); GnomAD homozygous count = 0.; Cumulative gnomAD AC = 10 (pure AD gene, not AR).

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>G p.Phe31Val	missense	Exon 3 of 9	Prot: NP_940839.1 UniProt:
	AURKA NM_001424418.1		c.193T>G p.Phe65Val	missense	Exon 5 of 11	Prot: NP_001411347.1
	AURKA NM_001424419.1		c.193T>G p.Phe65Val	missense	Exon 5 of 11	Prot: NP_001411348.1

AURKA NM_198437.3

MANE Select

HGVSc / HGVSpc.91T>Gp.Phe31Val

Exon rankExon 3 of 9

missense

Prot: NP_940839.1UniProt: O14965

AURKA NM_001424418.1

HGVSc / HGVSpc.193T>Gp.Phe65Val

Exon rankExon 5 of 11

missense

Prot: NP_001411347.1

AURKA NM_001424419.1

HGVSc / HGVSpc.193T>Gp.Phe65Val

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>G p.Phe31Val	missense	Exon 3 of 9	Prot: ENSP00000379251.3 UniProt:
	AURKA ENST00000312783.10	TSL:1	c.91T>G p.Phe31Val	missense	Exon 4 of 10	Prot: ENSP00000321591.6 UniProt:
	AURKA ENST00000347343.6	TSL:1	c.91T>G p.Phe31Val	missense	Exon 3 of 9	Prot: ENSP00000216911.2 UniProt:

AURKA ENST00000395915.8

TSL:1MANE Select

HGVSc / HGVSpc.91T>Gp.Phe31Val

Exon rankExon 3 of 9

missense

Prot: ENSP00000379251.3UniProt: O14965

AURKA ENST00000312783.10

TSL:1

HGVSc / HGVSpc.91T>Gp.Phe31Val

Exon rankExon 4 of 10

missense

Prot: ENSP00000321591.6UniProt: O14965

AURKA ENST00000347343.6

TSL:1

HGVSc / HGVSpc.91T>Gp.Phe31Val

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 5 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.00000658	AC:1	Hom:0	AN:152074	Cov:33
GnomAD4 exome	AF: 0.00000616	AC:9	Hom:0	AN:1461872	Cov:41
GnomAD4 genome	AF: 0.00000658	AC:1	Hom:0	AN:152074	Cov:33
TOPMed (Bravo)	AF: 0.00000378	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:988	AN:50362	Cov:

Showing 5 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
Epi25(Epilepsy)	0.00	0	41958	0.0000299	2	66888
SCHEMA(Schizophrenia)	0.0000129	1	77566	0.00	0	139118

Showing 2 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	7.3
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.59
DANN	Benign	0.32
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.10	N
FuncVEP CTI	Benign	0.00048
GPN-Star LLR	N/A	-3.9
GPN-Star score	N/A	3.9
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.99	T
Mutation Taster	N/A	96/4	polymorphism
PhyloP100	Benign	-0.56
popEVE	Benign	-3.5
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.075
Sift	Benign	0.66	T
Sift4G	Benign	0.50	T
VESM-3B	Benign	-1.5

Showing 26 of 26 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;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar