20-56386265-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_198437.3(AURKA):c.311C>T(p.Ser104Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000343 in 1,614,260 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00025 (5 hom.)
• Consequence: AURKA NM_198437.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.38

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004119545).
• BP6: Variant 20-56386265-G-A is Benign according to our data. Variant chr20-56386265-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3033554.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 194 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AURKA	NM_198437.3	c.311C>T	p.Ser104Leu	missense_variant	3/9	ENST00000395915.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AURKA	ENST00000395915.8	c.311C>T	p.Ser104Leu	missense_variant	3/9	1	NM_198437.3	P1

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 194 AN: 152250 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00415

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000994 AC: 250 AN: 251462 Hom.: 3 AF XY: 0.000758 AC XY: 103 AN XY: 135906

Gnomad AFR exome AF: 0.00492

Gnomad AMR exome AF: 0.00483

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000246 AC: 359 AN: 1461892 Hom.: 5 Cov.: 30 AF XY: 0.000226 AC XY: 164 AN XY: 727246

Gnomad4 AFR exome AF: 0.00514

Gnomad4 AMR exome AF: 0.00369

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.000215

GnomAD4 genome AF: 0.00127 AC: 194 AN: 152368 Hom.: 1 Cov.: 33 AF XY: 0.00109 AC XY: 81 AN XY: 74512

Gnomad4 AFR AF: 0.00414

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.000193 Hom.: 0

Bravo AF: 0.00173

ESP6500AA AF: 0.00454 AC: 20

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00101 AC: 123

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

AURKA-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 03, 2020

This variant is classified as likely 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
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	16
Dann	Uncertain	0.98
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.74	D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.0041	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.82	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N;N;N;N;N;N;D
REVEL	Benign	0.079
Sift	Benign	0.13	T;T;T;T;T;T;T;T;T;T;T;D
Sift4G	Benign	0.15	T;T;T;T;T;T;T;T;.;.;.;.
Polyphen		0.0020, 0.054, 0.18, 0.47, 0.072	.;.;.;.;.;.;.;B;B;B;P;B
Vest4		0.056
MVP		0.40
ClinPred		0.024	T
GERP RS		5.2
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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

Other links and lift over

dbSNP: rs2230743; hg19: chr20-54961321; COSMIC: COSV57168158; COSMIC: COSV57168158;