chr19-57231671-T-C

Position:

• chr19-57231671-T-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.59-71T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 1,568,290 control chromosomes in the GnomAD database, including 543,701 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (55531 hom., cov: 23)
  • Exomes 𝑓: 0.83 (488170 hom.)
• Consequence: AURKC ENST00000302804.12 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.73

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=-1.02).
• BP6: Variant 19-57231671-T-C is Benign according to our data. Variant chr19-57231671-T-C is described in ClinVar as [Benign]. Clinvar id is 1229063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AURKC	NM_001015878.2	c.59-71T>C		intron_variant		ENST00000302804.12	NP_001015878.1
AURKC	NM_001015879.2	c.2-71T>C		intron_variant			NP_001015879.1
AURKC	NM_003160.3	c.-44-71T>C		intron_variant			NP_003151.2
AURKC	XM_047439253.1	c.59-71T>C		intron_variant			XP_047295209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AURKC	ENST00000302804.12	c.59-71T>C		intron_variant		1	NM_001015878.2	ENSP00000302898	A2

Frequencies

GnomAD3 genomes AF: 0.860 AC: 128605 AN: 149626 Hom.: 55479 Cov.: 23

Gnomad AFR AF: 0.931

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.787

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.811

GnomAD4 exome AF: 0.829 AC: 1175894 AN: 1418546 Hom.: 488170 Cov.: 24 AF XY: 0.829 AC XY: 587348 AN XY: 708164

Gnomad4 AFR exome AF: 0.937

Gnomad4 AMR exome AF: 0.855

Gnomad4 ASJ exome AF: 0.850

Gnomad4 EAS exome AF: 0.840

Gnomad4 SAS exome AF: 0.866

Gnomad4 FIN exome AF: 0.896

Gnomad4 NFE exome AF: 0.818

Gnomad4 OTH exome AF: 0.831

GnomAD4 genome AF: 0.860 AC: 128713 AN: 149744 Hom.: 55531 Cov.: 23 AF XY: 0.862 AC XY: 62933 AN XY: 73024

Gnomad4 AFR AF: 0.931

Gnomad4 AMR AF: 0.834

Gnomad4 ASJ AF: 0.858

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.858

Gnomad4 FIN AF: 0.908

Gnomad4 NFE AF: 0.818

Gnomad4 OTH AF: 0.809

Alfa AF: 0.778 Hom.: 1804

Bravo AF: 0.860

Asia WGS AF: 0.826 AC: 2868 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.54

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: rs758098; hg19: chr19-57743039;