chr19-57231104-G-C

Position:

• chr19-57231104-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000302804.12(AURKC):​c.-145G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 1,454,604 control chromosomes in the GnomAD database, including 524,093 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (56277 hom., cov: 31)
  • Exomes 𝑓: 0.84 (467816 hom.)
• Consequence: AURKC ENST00000302804.12 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.22

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 19-57231104-G-C is Benign according to our data. Variant chr19-57231104-G-C is described in ClinVar as [Benign]. Clinvar id is 330224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-57231104-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AURKC	NM_001015878.2	c.-145G>C		5_prime_UTR_variant	1/7	ENST00000302804.12	NP_001015878.1
AURKC	NM_001015879.2	c.-10G>C		5_prime_UTR_variant	1/7		NP_001015879.1
AURKC	NM_003160.3	c.-60G>C		5_prime_UTR_variant	1/7		NP_003151.2
AURKC	XM_047439253.1	c.-145G>C		5_prime_UTR_variant	1/5		XP_047295209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AURKC	ENST00000302804.12	c.-145G>C		5_prime_UTR_variant	1/7	1	NM_001015878.2	ENSP00000302898	A2
AURKC	ENST00000415300.6	c.-10G>C		5_prime_UTR_variant	1/7	1		ENSP00000407162
AURKC	ENST00000601799.5			upstream_gene_variant		3		ENSP00000468918

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130435 AN: 151952 Hom.: 56225 Cov.: 31

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.813

GnomAD3 exomes AF: 0.870 AC: 114415 AN: 131524 Hom.: 53739 AF XY: 0.871 AC XY: 60209 AN XY: 69088

Gnomad AFR exome AF: 0.934

Gnomad AMR exome AF: 0.876

Gnomad ASJ exome AF: 0.879

Gnomad EAS exome AF: 0.855

Gnomad SAS exome AF: 0.895

Gnomad FIN exome AF: 0.930

Gnomad NFE exome AF: 0.834

Gnomad OTH exome AF: 0.829

GnomAD4 exome AF: 0.841 AC: 1095440 AN: 1302534 Hom.: 467816 Cov.: 35 AF XY: 0.842 AC XY: 541445 AN XY: 642976

Gnomad4 AFR exome AF: 0.940

Gnomad4 AMR exome AF: 0.865

Gnomad4 ASJ exome AF: 0.866

Gnomad4 EAS exome AF: 0.841

Gnomad4 SAS exome AF: 0.875

Gnomad4 FIN exome AF: 0.900

Gnomad4 NFE exome AF: 0.831

Gnomad4 OTH exome AF: 0.841

GnomAD4 genome AF: 0.858 AC: 130543 AN: 152070 Hom.: 56277 Cov.: 31 AF XY: 0.861 AC XY: 63964 AN XY: 74316

Gnomad4 AFR AF: 0.928

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.849

Gnomad4 SAS AF: 0.853

Gnomad4 FIN AF: 0.906

Gnomad4 NFE AF: 0.817

Gnomad4 OTH AF: 0.811

Alfa AF: 0.792 Hom.: 5966

Bravo AF: 0.859

Asia WGS AF: 0.829 AC: 2878 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.15
DANN	Benign	0.43

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: rs11084490; hg19: chr19-57742472; COSMIC: COSV57139544; COSMIC: COSV57139544;