NM_001015878.2:c.72C>A

Variant names:

• chr19-57231755-C-A
• rs780518366
• NM_001015878.2:c.72C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001015878.2(AURKC):​c.72C>A​(p.Asn24Lys) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: AURKC NM_001015878.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.739
• Publications: 0 publications found

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), Ambry Genetics, Laboratory for Molecular Medicine, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07254243).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001015878.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKC	NM_001015878.2	MANE Select	c.72C>A	p.Asn24Lys	missense	Exon 2 of 7	NP_001015878.1	Q9UQB9-1
	AURKC	NM_001015879.2		c.15C>A	p.Asn5Lys	missense	Exon 2 of 7	NP_001015879.1	Q9UQB9-3
	AURKC	NM_003160.3		c.-31C>A		5_prime_UTR	Exon 2 of 7	NP_003151.2	Q9UQB9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKC	ENST00000302804.12	TSL:1 MANE Select	c.72C>A	p.Asn24Lys	missense	Exon 2 of 7	ENSP00000302898.6	Q9UQB9-1
	AURKC	ENST00000599062.5	TSL:1	c.63C>A	p.Asn21Lys	missense	Exon 2 of 7	ENSP00000469983.1	Q5Y191
	AURKC	ENST00000415300.6	TSL:1	c.15C>A	p.Asn5Lys	missense	Exon 2 of 7	ENSP00000407162.1	Q9UQB9-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.61
DANN	Benign	0.42
DEOGEN2	Benign	0.091	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.74
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.050
Sift	Benign	0.56	T
Sift4G	Benign	0.79	T
Polyphen		0.0	B
Vest4		0.19
MutPred		0.31		Gain of ubiquitination at N24 (P = 4e-04)
MVP		0.61
MPC		0.21
ClinPred		0.098	T
GERP RS		-1.3
PromoterAI		0.19	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.086
gMVP		0.15
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs780518366; hg19: chr19-57743123;