Variant 1-1374332-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017900.3(AURKAIP1):c.166G>T(p.Ala56Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000319 in 1,567,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

AURKAIP1
NM_017900.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.671

Variant links:

Genes affected

AURKAIP1 (HGNC:24114): (aurora kinase A interacting protein 1) Acts upstream of or within positive regulation of proteolysis. Located in mitochondrion and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

AURKAIP1 links:

AURKAIP1 (HGNC:):

AURKAIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044991076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AURKAIP1	NM_017900.3 linkuse as main transcript	c.166G>T	p.Ala56Ser	missense_variant	3/4	ENST00000338338.10	NP_060370.1	Q9NWT8
AURKAIP1	NM_001127229.2 linkuse as main transcript	c.166G>T	p.Ala56Ser	missense_variant	3/4		NP_001120701.1	Q9NWT8
AURKAIP1	NM_001127230.2 linkuse as main transcript	c.166G>T	p.Ala56Ser	missense_variant	3/4		NP_001120702.1	Q9NWT8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AURKAIP1	ENST00000338338.10 linkuse as main transcript	c.166G>T	p.Ala56Ser	missense_variant	3/4	1	NM_017900.3	ENSP00000340656.5		Q9NWT8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000467

AC:

AN:

214330

Hom.:

AF XY:

0.00000850

AC XY:

AN XY:

117618

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000992

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000283

AC:

AN:

1415444

Hom.:

Cov.:

AF XY:

0.00000428

AC XY:

AN XY:

700302

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000183

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.166G>T (p.A56S) alteration is located in exon 3 (coding exon 2) of the AURKAIP1 gene. This alteration results from a G to T substitution at nucleotide position 166, causing the alanine (A) at amino acid position 56 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.92

DANN

Benign

0.65

DEOGEN2

Benign

0.017

T;T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.37

.;.;.;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.045

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;L;L;L

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.89

N;N;N;N

REVEL

Benign

0.032

Sift

Benign

0.40

T;T;T;T

Sift4G

Benign

0.40

T;T;T;T

Polyphen

0.0050

B;B;B;B

Vest4

0.049

MutPred

0.16

Gain of phosphorylation at A56 (P = 0.0174);Gain of phosphorylation at A56 (P = 0.0174);Gain of phosphorylation at A56 (P = 0.0174);Gain of phosphorylation at A56 (P = 0.0174);

MVP

0.34

MPC

0.27

ClinPred

0.023

GERP RS

-6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.049

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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