dbSNP rs1047972: AURKA:p.Ile57Phe (chr20-56386407-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198437.3(AURKA):c.169A>T(p.Ile57Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I57V) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AURKA
NM_198437.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.556

Publications

0 publications found

Variant links:

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

AURKA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKA	NM_198437.3 link	c.169A>T	p.Ile57Phe	missense_variant	Exon 3 of 9	ENST00000395915.8	NP_940839.1	O14965

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKA	ENST00000395915.8 link	c.169A>T	p.Ile57Phe	missense_variant	Exon 3 of 9	1	NM_198437.3	ENSP00000379251.3		O14965

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.84e-7

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112010

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

6.4

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.014

.;.;.;.;.;.;.;.;T;.;T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.054

.;.;.;.;.;.;.;T;T;T;T;T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.075

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.69

PhyloP100

-0.56

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.94

N;N;N;N;N;N;N;N;N;N;N;D;D

REVEL

Benign

0.072

Sift

Uncertain

0.0040

D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Benign

0.064

T;T;T;T;T;T;T;D;.;.;.;.;.

Polyphen

0.33, 0.21, 0.057, 0.045, 0.0

.;.;.;.;.;.;.;B;B;B;B;B;.

Vest4

0.13

MutPred

0.13

Loss of MoRF binding (P = 0.0873);Loss of MoRF binding (P = 0.0873);Loss of MoRF binding (P = 0.0873);Loss of MoRF binding (P = 0.0873);Loss of MoRF binding (P = 0.0873);Loss of MoRF binding (P = 0.0873);Loss of MoRF binding (P = 0.0873);Loss of MoRF binding (P = 0.0873);Loss of MoRF binding (P = 0.0873);Loss of MoRF binding (P = 0.0873);Loss of MoRF binding (P = 0.0873);Loss of MoRF binding (P = 0.0873);Loss of MoRF binding (P = 0.0873);

MVP

0.35

ClinPred

0.41

GERP RS

2.0

gMVP

0.34

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over