Genetic Variant AURKC:c.58+29A>T (chr19-57231335-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001015878.2(AURKC):c.58+29A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

AURKC
NM_001015878.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.807

Publications

9 publications found

Variant links:

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

AURKC links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
AURKC	NM_001015878.2 link	c.58+29A>T	intron_variant	Intron 1 of 6	ENST00000302804.12	NP_001015878.1	Q9UQB9-1
AURKC	NM_001015879.2 link	c.1+221A>T	intron_variant	Intron 1 of 6		NP_001015879.1	Q9UQB9-3
AURKC	NM_003160.3 link	c.-45+216A>T	intron_variant	Intron 1 of 6		NP_003151.2	Q9UQB9-2
AURKC	XM_047439253.1 link	c.58+29A>T	intron_variant	Intron 1 of 4		XP_047295209.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
AURKC	ENST00000302804.12 link	c.58+29A>T	intron_variant	Intron 1 of 6	1	NM_001015878.2	ENSP00000302898.6	Q9UQB9-1
AURKC	ENST00000599062.5 link	c.58+29A>T	intron_variant	Intron 1 of 6	1		ENSP00000469983.1	Q5Y191
AURKC	ENST00000415300.6 link	c.1+221A>T	intron_variant	Intron 1 of 6	1		ENSP00000407162.1	Q9UQB9-3
AURKC	ENST00000601799.5 link	n.87A>T	non_coding_transcript_exon_variant	Exon 1 of 6	3		ENSP00000468918.1	M0QX60

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000647

AC:

AN:

154544

AF XY:

0.0000123

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000402

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1399302

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31608

American (AMR)

AF:

0.0000558

AC:

AN:

35814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25184

East Asian (EAS)

AF:

0.00

AC:

AN:

35760

South Asian (SAS)

AF:

0.00

AC:

AN:

79240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48956

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5482

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1079234

Other (OTH)

AF:

0.00

AC:

AN:

58024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

1535

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.65

(source)

DANN

Benign

0.46

PhyloP100

-0.81

PromoterAI

-0.0060

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over