Genetic Variant AURKA:c.*3A>C (chr20-56370155-T-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_198437.3(AURKA):c.*3A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0211 in 1,612,342 control chromosomes in the GnomAD database, including 484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.016 ( 39 hom., cov: 32)

Exomes 𝑓: 0.022 ( 445 hom. )

Consequence

AURKA
NM_198437.3 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.29

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 20-56370155-T-G is Benign according to our data. Variant chr20-56370155-T-G is described in ClinVar as [Benign]. Clinvar id is 3037417.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0163 (2485/152334) while in subpopulation NFE AF= 0.0214 (1454/68034). AF 95% confidence interval is 0.0205. There are 39 homozygotes in gnomad4. There are 1337 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2485 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKA	NM_198437.3 link	c.*3A>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000395915.8	NP_940839.1	O14965

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKA	ENST00000395915 link	c.*3A>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_198437.3	ENSP00000379251.3		O14965

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2485

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00432

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.00851

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.0564

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0214

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.0187

AC:

4694

AN:

251408

Hom.:

AF XY:

0.0193

AC XY:

2625

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00394

Gnomad AMR exome

AF:

0.00838

Gnomad ASJ exome

AF:

0.00377

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0136

Gnomad FIN exome

AF:

0.0533

Gnomad NFE exome

AF:

0.0230

Gnomad OTH exome

AF:

0.0182

GnomAD4 exome

AF:

0.0216

AC:

31489

AN:

1460008

Hom.:

445

Cov.:

AF XY:

0.0213

AC XY:

15503

AN XY:

726308

show subpopulations

Gnomad4 AFR exome

AF:

0.00287

Gnomad4 AMR exome

AF:

0.00847

Gnomad4 ASJ exome

AF:

0.00390

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0136

Gnomad4 FIN exome

AF:

0.0498

Gnomad4 NFE exome

AF:

0.0232

Gnomad4 OTH exome

AF:

0.0203

GnomAD4 genome

AF:

0.0163

AC:

2485

AN:

152334

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

1337

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00430

Gnomad4 AMR

AF:

0.00849

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.0564

Gnomad4 NFE

AF:

0.0214

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0174

Hom.:

Bravo

AF:

0.0120

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0206

EpiControl

AF:

0.0213

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AURKA-related disorder

Benign:1

Oct 07, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.7

DANN

Benign

0.80

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over