Variant chr1-1373822-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The ENST00000338338.10(AURKAIP1):c.579G>T(p.Lys193Asn) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AURKAIP1
ENST00000338338.10 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.80

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 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=0.2442281).

BP6

Variant 1-1373822-C-A is Benign according to our data. Variant chr1-1373822-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2535931.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AURKAIP1	NM_017900.3 linkuse as main transcript	c.579G>T	p.Lys193Asn	missense_variant	4/4	ENST00000338338.10	NP_060370.1
AURKAIP1	NM_001127229.2 linkuse as main transcript	c.579G>T	p.Lys193Asn	missense_variant	4/4		NP_001120701.1
AURKAIP1	NM_001127230.2 linkuse as main transcript	c.579G>T	p.Lys193Asn	missense_variant	4/4		NP_001120702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
AURKAIP1	ENST00000338338.10 linkuse as main transcript	c.579G>T	p.Lys193Asn	missense_variant	4/4	1	NM_017900.3	ENSP00000340656	P1
AURKAIP1	ENST00000338370.7 linkuse as main transcript	c.579G>T	p.Lys193Asn	missense_variant	3/3	1		ENSP00000342676	P1
AURKAIP1	ENST00000321751.9 linkuse as main transcript	c.579G>T	p.Lys193Asn	missense_variant	4/4	2		ENSP00000319778	P1
AURKAIP1	ENST00000378853.3 linkuse as main transcript	c.579G>T	p.Lys193Asn	missense_variant	4/4	2		ENSP00000368130	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1449574

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721510

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:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 11, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.35

T;T;T;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.51

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.68

.;.;.;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.24

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.3

M;M;M;M

MutationTaster

Benign

0.91

D;D;D;D

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.5

D;D;D;D

REVEL

Benign

0.13

Sift

Benign

0.13

T;T;T;T

Sift4G

Benign

0.083

T;T;T;T

Polyphen

0.015

B;B;B;B

Vest4

0.35

MutPred

0.40

Loss of methylation at K193 (P = 0.0042);Loss of methylation at K193 (P = 0.0042);Loss of methylation at K193 (P = 0.0042);Loss of methylation at K193 (P = 0.0042);

MVP

0.51

MPC

0.36

ClinPred

0.63

GERP RS

2.6

Varity_R

0.30

gMVP

0.65

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over