chr19-57231259-C-G

Position:

• chr19-57231259-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000302804.12(AURKC):​c.11C>G​(p.Pro4Arg) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P4L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: AURKC ENST00000302804.12 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00200

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0868364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AURKC	NM_001015878.2	c.11C>G	p.Pro4Arg	missense_variant	1/7	ENST00000302804.12	NP_001015878.1
AURKC	XM_047439253.1	c.11C>G	p.Pro4Arg	missense_variant	1/5		XP_047295209.1
AURKC	NM_001015879.2	c.1+145C>G		intron_variant			NP_001015879.1
AURKC	NM_003160.3	c.-45+140C>G		intron_variant			NP_003151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AURKC	ENST00000302804.12	c.11C>G	p.Pro4Arg	missense_variant	1/7	1	NM_001015878.2	ENSP00000302898	A2
AURKC	ENST00000599062.5	c.11C>G	p.Pro4Arg	missense_variant	1/7	1		ENSP00000469983	P2
AURKC	ENST00000415300.6	c.1+145C>G		intron_variant		1		ENSP00000407162
AURKC	ENST00000601799.5	c.11C>G	p.Pro4Arg	missense_variant, NMD_transcript_variant	1/6	3		ENSP00000468918

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.11C>G (p.P4R) alteration is located in exon 1 (coding exon 1) of the AURKC gene. This alteration results from a C to G substitution at nucleotide position 11, causing the proline (P) at amino acid position 4 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	0.072
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.31
DANN	Benign	0.84
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.41	T;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.087	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.5	N;.
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D;.
Sift4G	Pathogenic	0.0010	D;T
Polyphen		0.047	B;B
Vest4		0.15
MutPred		0.24		Loss of glycosylation at P4 (P = 0.0313);Loss of glycosylation at P4 (P = 0.0313);
MVP		0.56
MPC		0.20
ClinPred		0.073	T
GERP RS		-3.5
Varity_R		0.085
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs553335951; hg19: chr19-57742627;