Variant 19-57231777-A-C 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_001015878.2(AURKC):c.94A>C(p.Ser32Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,826 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

AURKC
NM_001015878.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.36

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 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=0.056547374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AURKC	NM_001015878.2 linkuse as main transcript	c.94A>C	p.Ser32Arg	missense_variant	2/7	ENST00000302804.12	NP_001015878.1	Q9UQB9-1
AURKC	NM_001015879.2 linkuse as main transcript	c.37A>C	p.Ser13Arg	missense_variant	2/7		NP_001015879.1	Q9UQB9-3
AURKC	XM_047439253.1 linkuse as main transcript	c.94A>C	p.Ser32Arg	missense_variant	2/5		XP_047295209.1
AURKC	NM_003160.3 linkuse as main transcript	c.-9A>C		5_prime_UTR_variant	2/7		NP_003151.2	Q9UQB9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AURKC	ENST00000302804.12 linkuse as main transcript	c.94A>C	p.Ser32Arg	missense_variant	2/7	1	NM_001015878.2	ENSP00000302898.6		Q9UQB9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727212

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2024

The c.94A>C (p.S32R) alteration is located in exon 2 (coding exon 2) of the AURKC gene. This alteration results from a A to C substitution at nucleotide position 94, causing the serine (S) at amino acid position 32 to be replaced by an arginine (R). 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

0.21

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.046

DANN

Benign

0.31

DEOGEN2

Benign

0.10

.;T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0095

LIST_S2

Benign

0.25

T;T;T

M_CAP

Benign

0.00087

MetaRNN

Benign

0.057

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

.;N;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.98

N;N;.

REVEL

Benign

0.030

Sift

Benign

0.49

T;T;.

Sift4G

Benign

0.29

.;T;T

Polyphen

0.0

B;B;B

Vest4

0.15

MutPred

0.17

.;Loss of glycosylation at S32 (P = 0.0148);.;

MVP

0.23

MPC

0.20

ClinPred

0.033

GERP RS

-5.4

Varity_R

0.076

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