NM_001015878.2:c.-139C>T

Variant names:

• chr19-57231110-C-T
• rs138814299
• NM_001015878.2:c.-139C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001015878.2(AURKC):​c.-139C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000316 in 1,529,968 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00031 (1 hom.)
• Consequence: AURKC NM_001015878.2 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.05

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKC	NM_001015878.2	c.-139C>T		5_prime_UTR_variant	Exon 1 of 7	ENST00000302804.12	NP_001015878.1
AURKC	NM_001015879.2	c.-4C>T		5_prime_UTR_variant	Exon 1 of 7		NP_001015879.1
AURKC	NM_003160.3	c.-54C>T		5_prime_UTR_variant	Exon 1 of 7		NP_003151.2
AURKC	XM_047439253.1	c.-139C>T		5_prime_UTR_variant	Exon 1 of 5		XP_047295209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKC	ENST00000302804	c.-139C>T		5_prime_UTR_variant	Exon 1 of 7	1	NM_001015878.2	ENSP00000302898.6
AURKC	ENST00000415300	c.-4C>T		5_prime_UTR_variant	Exon 1 of 7	1		ENSP00000407162.1
AURKC	ENST00000599062.5	c.-139C>T		upstream_gene_variant		1		ENSP00000469983.1
AURKC	ENST00000601799.5	n.-139C>T		upstream_gene_variant		3		ENSP00000468918.1

Frequencies

GnomAD3 genomes AF: 0.000337 AC: 51 AN: 151196 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00727

Gnomad SAS AF: 0.00168

Gnomad FIN AF: 0.0000963

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000860 AC: 114 AN: 132630 Hom.: 1 AF XY: 0.000855 AC XY: 60 AN XY: 70144

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000439

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00747

Gnomad SAS exome AF: 0.00144

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000399

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000314 AC: 433 AN: 1378652 Hom.: 1 Cov.: 38 AF XY: 0.000338 AC XY: 230 AN XY: 680854

Gnomad4 AFR exome AF: 0.0000319

Gnomad4 AMR exome AF: 0.0000280

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00717

Gnomad4 SAS exome AF: 0.00126

Gnomad4 FIN exome AF: 0.000102

Gnomad4 NFE exome AF: 0.0000189

Gnomad4 OTH exome AF: 0.000889

GnomAD4 genome AF: 0.000337 AC: 51 AN: 151316 Hom.: 0 Cov.: 31 AF XY: 0.000379 AC XY: 28 AN XY: 73858

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00729

Gnomad4 SAS AF: 0.00168

Gnomad4 FIN AF: 0.0000963

Gnomad4 NFE AF: 0.0000736

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000378 Hom.: 0

Bravo AF: 0.000389

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Infertility associated with multi-tailed spermatozoa and excessive DNA Uncertain:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs138814299; hg19: chr19-57742478;