chr19-57231671-T-C

Variant names:

• chr19-57231671-T-C
• rs758098
• ENST00000598785.5:c.-115T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001015878.2(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 NM_001015878.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.73
• Publications: 3 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
AURKC	NM_001015878.2	c.59-71T>C		intron_variant	Intron 1 of 6	ENST00000302804.12	NP_001015878.1
AURKC	NM_001015879.2	c.2-71T>C		intron_variant	Intron 1 of 6		NP_001015879.1
AURKC	NM_003160.3	c.-44-71T>C		intron_variant	Intron 1 of 6		NP_003151.2
AURKC	XM_047439253.1	c.59-71T>C		intron_variant	Intron 1 of 4		XP_047295209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKC	ENST00000302804.12	c.59-71T>C		intron_variant	Intron 1 of 6	1	NM_001015878.2	ENSP00000302898.6

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

African (AFR) AF: 0.937 AC: 30453 AN: 32494

American (AMR) AF: 0.855 AC: 37476 AN: 43832

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 21924 AN: 25800

East Asian (EAS) AF: 0.840 AC: 33073 AN: 39392

South Asian (SAS) AF: 0.866 AC: 73793 AN: 85248

European-Finnish (FIN) AF: 0.896 AC: 47632 AN: 53146

Middle Eastern (MID) AF: 0.772 AC: 4374 AN: 5666

European-Non Finnish (NFE) AF: 0.818 AC: 878223 AN: 1074046

Other (OTH) AF: 0.831 AC: 48946 AN: 58922

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

African (AFR) AF: 0.931 AC: 37759 AN: 40552

American (AMR) AF: 0.834 AC: 12479 AN: 14956

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2959 AN: 3450

East Asian (EAS) AF: 0.853 AC: 4249 AN: 4980

South Asian (SAS) AF: 0.858 AC: 4034 AN: 4704

European-Finnish (FIN) AF: 0.908 AC: 9366 AN: 10318

Middle Eastern (MID) AF: 0.808 AC: 236 AN: 292

European-Non Finnish (NFE) AF: 0.818 AC: 55211 AN: 67500

Other (OTH) AF: 0.809 AC: 1693 AN: 2092

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

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.54
PhyloP100		-1.7
PromoterAI		0.092	Neutral
Mutation Taster		=115/185	disease causing

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: rs758098; hg19: chr19-57743039;