NM_001015878.2:c.12C>G

Variant names:

• chr19-57231260-C-G
• rs73633650
• NM_001015878.2:c.12C>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001015878.2(AURKC):​c.12C>G​(p.Pro4Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000418 in 1,552,262 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (3 hom., cov: 30)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: AURKC NM_001015878.2 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.781
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-0.781 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.12C>G	p.Pro4Pro	synonymous	Exon 1 of 7	NP_001015878.1	Q9UQB9-1
	AURKC	NM_001015879.2		c.1+146C>G		intron	N/A	NP_001015879.1	Q9UQB9-3
	AURKC	NM_003160.3		c.-45+141C>G		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.12C>G	p.Pro4Pro	synonymous	Exon 1 of 7	ENSP00000302898.6	Q9UQB9-1
	AURKC	ENST00000599062.5	TSL:1	c.12C>G	p.Pro4Pro	synonymous	Exon 1 of 7	ENSP00000469983.1	Q5Y191
	AURKC	ENST00000415300.6	TSL:1	c.1+146C>G		intron	N/A	ENSP00000407162.1	Q9UQB9-3

Frequencies

GnomAD3 genomes AF: 0.00206 AC: 314 AN: 152106 Hom.: 3 Cov.: 30

Gnomad AFR AF: 0.00717

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000508 AC: 79 AN: 155502 AF XY: 0.000390

Gnomad AFR exome AF: 0.00629

Gnomad AMR exome AF: 0.000562

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000169

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000238 AC: 333 AN: 1400038 Hom.: 0 Cov.: 41 AF XY: 0.000222 AC XY: 153 AN XY: 690574

African (AFR) AF: 0.00749 AC: 237 AN: 31622

American (AMR) AF: 0.000558 AC: 20 AN: 35850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25184

East Asian (EAS) AF: 0.00 AC: 0 AN: 35762

South Asian (SAS) AF: 0.000341 AC: 27 AN: 79254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49366

Middle Eastern (MID) AF: 0.000527 AC: 3 AN: 5698

European-Non Finnish (NFE) AF: 0.0000222 AC: 24 AN: 1079270

Other (OTH) AF: 0.000379 AC: 22 AN: 58032

GnomAD4 genome AF: 0.00208 AC: 316 AN: 152224 Hom.: 3 Cov.: 30 AF XY: 0.00192 AC XY: 143 AN XY: 74440

African (AFR) AF: 0.00720 AC: 299 AN: 41534

American (AMR) AF: 0.000719 AC: 11 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68002

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.000675 Hom.: 1

Bravo AF: 0.00209

Asia WGS AF: 0.000866 AC: 4 AN: 3478

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	-0.90
CADD	Benign	0.33
DANN	Benign	0.42
PhyloP100		-0.78
PromoterAI		0.035	Neutral
Mutation Taster		=100/0	polymorphism

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: rs73633650; hg19: chr19-57742628;