19-57231966-C-T

Variant names:

• chr19-57231966-C-T
• rs758099
• NM_001015878.2:c.105-67C>T

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.105-67C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,604,894 control chromosomes in the GnomAD database, including 83,949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7978 hom., cov: 31)
  • Exomes 𝑓: 0.31 (75971 hom.)
• Consequence: AURKC NM_001015878.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.32
• Publications: 18 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=-0.92).
• BP6: Variant 19-57231966-C-T is Benign according to our data. Variant chr19-57231966-C-T is described in ClinVar as [Benign]. Clinvar id is 1248562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKC	NM_001015878.2	c.105-67C>T		intron_variant	Intron 2 of 6	ENST00000302804.12	NP_001015878.1
AURKC	NM_001015879.2	c.48-67C>T		intron_variant	Intron 2 of 6		NP_001015879.1
AURKC	NM_003160.3	c.3-67C>T		intron_variant	Intron 2 of 6		NP_003151.2
AURKC	XM_047439253.1	c.105-67C>T		intron_variant	Intron 2 of 4		XP_047295209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKC	ENST00000302804.12	c.105-67C>T		intron_variant	Intron 2 of 6	1	NM_001015878.2	ENSP00000302898.6

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47276 AN: 151740 Hom.: 7970 Cov.: 31

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.315 AC: 457380 AN: 1453034 Hom.: 75971 Cov.: 32 AF XY: 0.315 AC XY: 227747 AN XY: 723436

African (AFR) AF: 0.280 AC: 9323 AN: 33272

American (AMR) AF: 0.408 AC: 18226 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 7970 AN: 26084

East Asian (EAS) AF: 0.687 AC: 27253 AN: 39662

South Asian (SAS) AF: 0.354 AC: 30434 AN: 85932

European-Finnish (FIN) AF: 0.340 AC: 18113 AN: 53268

Middle Eastern (MID) AF: 0.267 AC: 1447 AN: 5410

European-Non Finnish (NFE) AF: 0.294 AC: 324878 AN: 1104694

Other (OTH) AF: 0.329 AC: 19736 AN: 60076

GnomAD4 genome AF: 0.312 AC: 47325 AN: 151860 Hom.: 7978 Cov.: 31 AF XY: 0.317 AC XY: 23520 AN XY: 74222

African (AFR) AF: 0.282 AC: 11696 AN: 41432

American (AMR) AF: 0.350 AC: 5340 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1090 AN: 3470

East Asian (EAS) AF: 0.684 AC: 3499 AN: 5118

South Asian (SAS) AF: 0.366 AC: 1758 AN: 4806

European-Finnish (FIN) AF: 0.356 AC: 3754 AN: 10534

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19348 AN: 67930

Other (OTH) AF: 0.293 AC: 617 AN: 2106

Alfa AF: 0.294 Hom.: 17511

Bravo AF: 0.313

Asia WGS AF: 0.475 AC: 1650 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.59
PhyloP100		-1.3
PromoterAI		0.046	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs758099; hg19: chr19-57743334; COSMIC: COSV57138836; COSMIC: COSV57138836;