Variant 1-1374091-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_017900.3(AURKAIP1):c.407G>A(p.Arg136Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Consequence

AURKAIP1
NM_017900.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.34

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.835

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AURKAIP1	NM_017900.3 linkuse as main transcript	c.407G>A	p.Arg136Gln	missense_variant	3/4	ENST00000338338.10	NP_060370.1	Q9NWT8
AURKAIP1	NM_001127229.2 linkuse as main transcript	c.407G>A	p.Arg136Gln	missense_variant	3/4		NP_001120701.1	Q9NWT8
AURKAIP1	NM_001127230.2 linkuse as main transcript	c.407G>A	p.Arg136Gln	missense_variant	3/4		NP_001120702.1	Q9NWT8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AURKAIP1	ENST00000338338.10 linkuse as main transcript	c.407G>A	p.Arg136Gln	missense_variant	3/4	1	NM_017900.3	ENSP00000340656.5	Q9NWT8
AURKAIP1	ENST00000338370.7 linkuse as main transcript	c.407G>A	p.Arg136Gln	missense_variant	2/3	1		ENSP00000342676.3	Q9NWT8
AURKAIP1	ENST00000321751.9 linkuse as main transcript	c.407G>A	p.Arg136Gln	missense_variant	3/4	2		ENSP00000319778.5	Q9NWT8
AURKAIP1	ENST00000378853.3 linkuse as main transcript	c.407G>A	p.Arg136Gln	missense_variant	3/4	2		ENSP00000368130.3	Q9NWT8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

May 26, 2023

The c.407G>A (p.R136Q) alteration is located in exon 3 (coding exon 2) of the AURKAIP1 gene. This alteration results from a G to A substitution at nucleotide position 407, causing the arginine (R) at amino acid position 136 to be replaced by a glutamine (Q). 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

Uncertain

0.44

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.47

T;T;T;T

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

.;.;.;D

M_CAP

Benign

0.040

MetaRNN

Pathogenic

0.84

D;D;D;D

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.9

L;L;L;L

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.2

D;D;D;D

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Uncertain

0.014

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.74

MutPred

0.65

Loss of catalytic residue at K137 (P = 0.0958);Loss of catalytic residue at K137 (P = 0.0958);Loss of catalytic residue at K137 (P = 0.0958);Loss of catalytic residue at K137 (P = 0.0958);

MVP

0.85

MPC

0.61

ClinPred

0.99

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.74

gMVP

0.40

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

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