chr20-56386407-T-C

Variant names:

• chr20-56386407-T-C
• rs1047972
• NM_198437.3:c.169A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_198437.3(AURKA):​c.169A>G​(p.Ile57Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 1,613,986 control chromosomes in the GnomAD database, including 575,145 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.84 (54283 hom., cov: 31)
  • Exomes 𝑓: 0.84 (520862 hom.)
• Consequence: AURKA NM_198437.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.556

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.0621073E-7).
• BP6: Variant 20-56386407-T-C is Benign according to our data. Variant chr20-56386407-T-C is described in ClinVar as [Benign]. Clinvar id is 3059051.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKA	NM_198437.3	c.169A>G	p.Ile57Val	missense_variant	Exon 3 of 9	ENST00000395915.8	NP_940839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKA	ENST00000395915.8	c.169A>G	p.Ile57Val	missense_variant	Exon 3 of 9	1	NM_198437.3	ENSP00000379251.3

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128366 AN: 152010 Hom.: 54229 Cov.: 31

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.892

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.865

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.860

GnomAD2 exomes AF: 0.851 AC: 213970 AN: 251486 AF XY: 0.848

Gnomad AFR exome AF: 0.839

Gnomad AMR exome AF: 0.916

Gnomad ASJ exome AF: 0.853

Gnomad EAS exome AF: 0.878

Gnomad FIN exome AF: 0.807

Gnomad NFE exome AF: 0.835

Gnomad OTH exome AF: 0.842

GnomAD4 exome AF: 0.844 AC: 1233537 AN: 1461858 Hom.: 520862 Cov.: 88 AF XY: 0.844 AC XY: 613833 AN XY: 727230

Gnomad4 AFR exome AF: 0.834 AC: 27934 AN: 33480

Gnomad4 AMR exome AF: 0.912 AC: 40766 AN: 44722

Gnomad4 ASJ exome AF: 0.858 AC: 22435 AN: 26136

Gnomad4 EAS exome AF: 0.871 AC: 34571 AN: 39700

Gnomad4 SAS exome AF: 0.858 AC: 73996 AN: 86258

Gnomad4 FIN exome AF: 0.810 AC: 43274 AN: 53420

Gnomad4 NFE exome AF: 0.840 AC: 934582 AN: 1111978

Gnomad4 Remaining exome AF: 0.847 AC: 51160 AN: 60396

GnomAD4 genome AF: 0.845 AC: 128476 AN: 152128 Hom.: 54283 Cov.: 31 AF XY: 0.843 AC XY: 62696 AN XY: 74386

Gnomad4 AFR AF: 0.838 AC: 0.838025 AN: 0.838025

Gnomad4 AMR AF: 0.887 AC: 0.887392 AN: 0.887392

Gnomad4 ASJ AF: 0.865 AC: 0.865207 AN: 0.865207

Gnomad4 EAS AF: 0.880 AC: 0.880372 AN: 0.880372

Gnomad4 SAS AF: 0.855 AC: 0.855394 AN: 0.855394

Gnomad4 FIN AF: 0.810 AC: 0.810182 AN: 0.810182

Gnomad4 NFE AF: 0.838 AC: 0.83848 AN: 0.83848

Gnomad4 OTH AF: 0.856 AC: 0.855724 AN: 0.855724

Alfa AF: 0.840 Hom.: 263613

Bravo AF: 0.850

TwinsUK AF: 0.841 AC: 3119

ALSPAC AF: 0.847 AC: 3265

ESP6500AA AF: 0.838 AC: 3693

ESP6500EA AF: 0.838 AC: 7203

ExAC AF: 0.848 AC: 102977

Asia WGS AF: 0.872 AC: 3034 AN: 3478

EpiCase AF: 0.829

EpiControl AF: 0.826

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

AURKA-related disorder Benign:1

Oct 17, 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
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.032
DANN	Benign	0.21
DEOGEN2	Benign	0.0047	.;.;.;.;.;.;.;.;T;.;T;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.016	.;.;.;.;.;.;.;T;T;T;T;T;T
MetaRNN	Benign	6.1e-7	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.010	N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.031
Sift	Benign	1.0	T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T;.;.;.;.;.
Polyphen		0.0	.;.;.;.;.;.;.;B;B;B;B;B;.
Vest4		0.010
ClinPred		0.00020	T
GERP RS		2.0
gMVP		0.092
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1047972; hg19: chr20-54961463; COSMIC: COSV100452806;