rs2122802289

Variant names:

• chr19-57232046-G-A
• rs2122802289
• NM_001015878.2:c.118G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-57232046-G-A
• chr19-57232046-G-C

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.118G>A​(p.Val40Ile) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V40L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: AURKC NM_001015878.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.55
• 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), Orphanet, Laboratory for Molecular Medicine, Ambry Genetics

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=0.10323551).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKC	NM_001015878.2	c.118G>A	p.Val40Ile	missense_variant	Exon 3 of 7	ENST00000302804.12	NP_001015878.1
AURKC	NM_001015879.2	c.61G>A	p.Val21Ile	missense_variant	Exon 3 of 7		NP_001015879.1
AURKC	NM_003160.3	c.16G>A	p.Val6Ile	missense_variant	Exon 3 of 7		NP_003151.2
AURKC	XM_047439253.1	c.118G>A	p.Val40Ile	missense_variant	Exon 3 of 5		XP_047295209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKC	ENST00000302804.12	c.118G>A	p.Val40Ile	missense_variant	Exon 3 of 7	1	NM_001015878.2	ENSP00000302898.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.0
DANN	Benign	0.53
DEOGEN2	Benign	0.060	.;.;T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.61	T;T;T;T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.10	T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	.;.;N;.;.
PhyloP100		2.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.86	N;N;N;.;.
REVEL	Benign	0.11
Sift	Benign	0.48	T;T;T;.;.
Sift4G	Benign	0.40	.;.;T;T;.
Polyphen		0.0	.;B;B;B;.
Vest4		0.16
MutPred		0.45		.;.;Gain of loop (P = 0.2045);.;.;
MVP		0.38
MPC		0.14
ClinPred		0.23	T
GERP RS		2.8
PromoterAI		0.031	Neutral
Varity_R		0.085
gMVP		0.094
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs2122802289; hg19: chr19-57743414;