Variant 1-1374156-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000338338.10(AURKAIP1):c.342G>C(p.Gln114His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

AURKAIP1
ENST00000338338.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0670

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.18894565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AURKAIP1	NM_017900.3 linkuse as main transcript	c.342G>C	p.Gln114His	missense_variant	3/4	ENST00000338338.10	NP_060370.1
AURKAIP1	NM_001127229.2 linkuse as main transcript	c.342G>C	p.Gln114His	missense_variant	3/4		NP_001120701.1
AURKAIP1	NM_001127230.2 linkuse as main transcript	c.342G>C	p.Gln114His	missense_variant	3/4		NP_001120702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
AURKAIP1	ENST00000338338.10 linkuse as main transcript	c.342G>C	p.Gln114His	missense_variant	3/4	1	NM_017900.3	ENSP00000340656	P1
AURKAIP1	ENST00000338370.7 linkuse as main transcript	c.342G>C	p.Gln114His	missense_variant	2/3	1		ENSP00000342676	P1
AURKAIP1	ENST00000321751.9 linkuse as main transcript	c.342G>C	p.Gln114His	missense_variant	3/4	2		ENSP00000319778	P1
AURKAIP1	ENST00000378853.3 linkuse as main transcript	c.342G>C	p.Gln114His	missense_variant	3/4	2		ENSP00000368130	P1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152266

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251242

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135810

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:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461620

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000629

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74390

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.00000824

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

Oct 03, 2022

The c.342G>C (p.Q114H) alteration is located in exon 3 (coding exon 2) of the AURKAIP1 gene. This alteration results from a G to C substitution at nucleotide position 342, causing the glutamine (Q) at amino acid position 114 to be replaced by a histidine (H). 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

0.15

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.043

T;T;T;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.44

.;.;.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.19

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M;M;M

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.0

N;N;N;N

REVEL

Benign

0.053

Sift

Benign

0.061

T;T;T;T

Sift4G

Benign

0.16

T;T;T;T

Polyphen

0.94

P;P;P;P

Vest4

0.16

MutPred

0.16

Gain of catalytic residue at Q114 (P = 0.1295);Gain of catalytic residue at Q114 (P = 0.1295);Gain of catalytic residue at Q114 (P = 0.1295);Gain of catalytic residue at Q114 (P = 0.1295);

MVP

0.75

MPC

0.28

ClinPred

0.089

GERP RS

3.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.080

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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