19-57231671-T-A

Variant names:

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

Variant summary

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

The ENST00000598785.5(AURKC):​c.-115T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 23)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AURKC ENST00000598785.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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), 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=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000598785.5. 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.59-71T>A		intron	N/A	NP_001015878.1	Q9UQB9-1
	AURKC	NM_001015879.2		c.2-71T>A		intron	N/A	NP_001015879.1	Q9UQB9-3
	AURKC	NM_003160.3		c.-44-71T>A		intron	N/A	NP_003151.2	Q9UQB9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKC	ENST00000598785.5	TSL:1	c.-115T>A		5_prime_UTR	Exon 1 of 6	ENSP00000471830.1	Q9UQB9-2
	AURKC	ENST00000302804.12	TSL:1 MANE Select	c.59-71T>A		intron	N/A	ENSP00000302898.6	Q9UQB9-1
	AURKC	ENST00000599062.5	TSL:1	c.59-80T>A		intron	N/A	ENSP00000469983.1	Q5Y191

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1419424 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 708550

African (AFR) AF: 0.00 AC: 0 AN: 32508

American (AMR) AF: 0.00 AC: 0 AN: 43838

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25804

East Asian (EAS) AF: 0.00 AC: 0 AN: 39400

South Asian (SAS) AF: 0.00 AC: 0 AN: 85260

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5670

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1074820

Other (OTH) AF: 0.00 AC: 0 AN: 58960

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.48
PhyloP100		-1.7
PromoterAI		-0.085	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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;