rs1047972

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-56386407-T-A
• chr20-56386407-T-C
• chr20-56386407-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 12/19 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 Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AURKA NM_198437.3 missense
• Clinical Significance: Not reported in ClinVar
• 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

Verdict is Uncertain_significance. Variant got 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	c.169A>T	p.Ile57Phe	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>T	p.Ile57Phe	missense_variant	Exon 3 of 9	1	NM_198437.3	ENSP00000379251.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 88 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

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	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.4
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	N
LIST_S2	Benign	0.054	.;.;.;.;.;.;.;T;T;T;T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.075	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.69	T
PrimateAI	Benign	0.28	T
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	T
GERP RS		2.0
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-54961463;