19-57231196-A-C

Variant names:

• chr19-57231196-A-C
• rs2087484333
• NM_001015878.2:c.-53A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001015878.2(AURKC):​c.-53A>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 0.00000643 in 1,399,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: AURKC NM_001015878.2 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.75
• Publications: 0 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), Ambry Genetics, Laboratory for Molecular Medicine, Orphanet

ACMG classification

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=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001015878.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKC	NM_001015878.2	MANE Select	c.-53A>C		5_prime_UTR	Exon 1 of 7	NP_001015878.1	Q9UQB9-1
	AURKC	NM_001015879.2		c.1+82A>C		intron	N/A	NP_001015879.1	Q9UQB9-3
	AURKC	NM_003160.3		c.-45+77A>C		intron	N/A	NP_003151.2	Q9UQB9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKC	ENST00000302804.12	TSL:1 MANE Select	c.-53A>C		5_prime_UTR	Exon 1 of 7	ENSP00000302898.6	Q9UQB9-1
	AURKC	ENST00000415300.6	TSL:1	c.1+82A>C		intron	N/A	ENSP00000407162.1	Q9UQB9-3
	AURKC	ENST00000923144.1		c.-53A>C		5_prime_UTR	Exon 1 of 7	ENSP00000593203.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000643 AC: 9 AN: 1399318 Hom.: 0 Cov.: 41 AF XY: 0.00000724 AC XY: 5 AN XY: 690168

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35670

South Asian (SAS) AF: 0.00 AC: 0 AN: 79238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000834 AC: 9 AN: 1078944

Other (OTH) AF: 0.00 AC: 0 AN: 58000

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Infertility associated with multi-tailed spermatozoa and excessive DNA (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.60
PhyloP100		-1.7
PromoterAI		-0.076	Neutral

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

Other links and lift over

dbSNP: rs2087484333; hg19: chr19-57742564;