19-57231261-A-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001015878.2(AURKC):c.13A>G(p.Arg5Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000374 in 1,551,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

AURKC
NM_001015878.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.60

Publications

0 publications found

Variant links:

Genes affected

AURKC (HGNC:11391): (aurora kinase C) This gene encodes a member of the Aurora subfamily of serine/threonine protein kinases. The encoded protein is a chromosomal passenger protein that forms complexes with Aurora-B and inner centromere proteins and may play a role in organizing microtubules in relation to centrosome/spindle function during mitosis. This gene is overexpressed in several cancer cell lines, suggesting an involvement in oncogenic signal transduction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

AURKC Gene-Disease associations (from GenCC):

spermatogenic failure 5
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine, Ambry Genetics

AURKC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01695025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKC	NM_001015878.2 link	c.13A>G	p.Arg5Gly	missense_variant	Exon 1 of 7	ENST00000302804.12	NP_001015878.1	Q9UQB9-1
AURKC	XM_047439253.1 link	c.13A>G	p.Arg5Gly	missense_variant	Exon 1 of 5		XP_047295209.1
AURKC	NM_001015879.2 link	c.1+147A>G		intron_variant	Intron 1 of 6		NP_001015879.1	Q9UQB9-3
AURKC	NM_003160.3 link	c.-45+142A>G		intron_variant	Intron 1 of 6		NP_003151.2	Q9UQB9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AURKC	ENST00000302804.12 link	c.13A>G	p.Arg5Gly	missense_variant	Exon 1 of 7	1	NM_001015878.2	ENSP00000302898.6	Q9UQB9-1
AURKC	ENST00000599062.5 link	c.13A>G	p.Arg5Gly	missense_variant	Exon 1 of 7	1		ENSP00000469983.1	Q5Y191
AURKC	ENST00000415300.6 link	c.1+147A>G		intron_variant	Intron 1 of 6	1		ENSP00000407162.1	Q9UQB9-3
AURKC	ENST00000601799.5 link	n.13A>G		non_coding_transcript_exon_variant	Exon 1 of 6	3		ENSP00000468918.1	M0QX60

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

151766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000387

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

GnomAD2 exomes

AF:

0.0000386

AC:

AN:

155560

AF XY:

0.0000244

show subpopulations

Gnomad AFR exome

AF:

0.000674

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000300

AC:

AN:

1400054

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

690584

show subpopulations

African (AFR)

AF:

0.000759

AC:

AN:

31622

American (AMR)

AF:

0.00

AC:

AN:

35848

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25184

East Asian (EAS)

AF:

0.00

AC:

AN:

35762

South Asian (SAS)

AF:

0.00

AC:

AN:

79256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49368

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00000741

AC:

AN:

1079280

Other (OTH)

AF:

0.000138

AC:

AN:

58036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000105

AC:

AN:

151882

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.000386

AC:

AN:

41416

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5106

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67926

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.556

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000219

Hom.:

Bravo

AF:

0.000155

ESP6500AA

AF:

0.000233

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000408

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Jan 04, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.13A>G (p.R5G) alteration is located in exon 1 (coding exon 1) of the AURKC gene. This alteration results from a A to G substitution at nucleotide position 13, causing the arginine (R) at amino acid position 5 to be replaced by a glycine (G). 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

0.16

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.090

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.085

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.35

T;T

M_CAP

Benign

0.0087

MetaRNN

Benign

0.017

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

PhyloP100

-3.6

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.30

N;.

REVEL

Benign

0.058

Sift

Benign

0.38

T;.

Sift4G

Benign

0.37

T;T

Polyphen

0.0

B;B

Vest4

0.11

MVP

0.38

MPC

0.23

ClinPred

0.015

GERP RS

-4.7

PromoterAI

0.14

Neutral

(source)

Varity_R

0.041

gMVP

0.43

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

19-57231261-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over