rs1047972

Variant names:

• chr20-56386407-T-A
• rs1047972
• 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. The variant received 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556
• Publications: 0 publications found

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

ACMG classification

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198437.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKA	NM_198437.3	MANE Select	c.169A>T	p.Ile57Phe	missense	Exon 3 of 9	NP_940839.1	O14965
	AURKA	NM_001424418.1		c.271A>T	p.Ile91Phe	missense	Exon 5 of 11	NP_001411347.1
	AURKA	NM_001424419.1		c.271A>T	p.Ile91Phe	missense	Exon 5 of 11	NP_001411348.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKA	ENST00000395915.8	TSL:1 MANE Select	c.169A>T	p.Ile57Phe	missense	Exon 3 of 9	ENSP00000379251.3	O14965
	AURKA	ENST00000312783.10	TSL:1	c.169A>T	p.Ile57Phe	missense	Exon 4 of 10	ENSP00000321591.6	O14965
	AURKA	ENST00000347343.6	TSL:1	c.169A>T	p.Ile57Phe	missense	Exon 3 of 9	ENSP00000216911.2	O14965

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.054	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.69	T
PhyloP100		-0.56
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.072
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.064	T
Polyphen		0.33	B
Vest4		0.13
MutPred		0.13		Loss of MoRF binding (P = 0.0873)
MVP		0.35
ClinPred		0.41	T
GERP RS		2.0
gMVP		0.34
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs1047972; hg19: chr20-54961463;