chr19-57231335-A-G

Variant names:

• chr19-57231335-A-G
• rs758097
• NM_001015878.2:c.58+29A>G

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.58+29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,550,982 control chromosomes in the GnomAD database, including 82,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8529 hom., cov: 30)
  • Exomes 𝑓: 0.32 (73838 hom.)
• Consequence: AURKC NM_001015878.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.807
• Publications: 9 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=-0.9).
• BP6: Variant 19-57231335-A-G is Benign according to our data. Variant chr19-57231335-A-G is described in ClinVar as [Benign]. Clinvar id is 1257509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49149 AN: 151704 Hom.: 8520 Cov.: 30

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.303

GnomAD2 exomes AF: 0.358 AC: 55261 AN: 154544 AF XY: 0.353

Gnomad AFR exome AF: 0.318

Gnomad AMR exome AF: 0.410

Gnomad ASJ exome AF: 0.302

Gnomad EAS exome AF: 0.693

Gnomad FIN exome AF: 0.348

Gnomad NFE exome AF: 0.291

Gnomad OTH exome AF: 0.313

GnomAD4 exome AF: 0.317 AC: 443307 AN: 1399160 Hom.: 73838 Cov.: 41 AF XY: 0.317 AC XY: 218719 AN XY: 690158

African (AFR) AF: 0.320 AC: 10112 AN: 31608

American (AMR) AF: 0.407 AC: 14561 AN: 35814

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 7701 AN: 25184

East Asian (EAS) AF: 0.689 AC: 24638 AN: 35760

South Asian (SAS) AF: 0.357 AC: 28315 AN: 79238

European-Finnish (FIN) AF: 0.340 AC: 16650 AN: 48926

Middle Eastern (MID) AF: 0.277 AC: 1518 AN: 5478

European-Non Finnish (NFE) AF: 0.297 AC: 320374 AN: 1079132

Other (OTH) AF: 0.335 AC: 19438 AN: 58020

GnomAD4 genome AF: 0.324 AC: 49205 AN: 151822 Hom.: 8529 Cov.: 30 AF XY: 0.329 AC XY: 24387 AN XY: 74194

African (AFR) AF: 0.320 AC: 13239 AN: 41422

American (AMR) AF: 0.355 AC: 5413 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1084 AN: 3470

East Asian (EAS) AF: 0.689 AC: 3505 AN: 5090

South Asian (SAS) AF: 0.370 AC: 1781 AN: 4812

European-Finnish (FIN) AF: 0.357 AC: 3757 AN: 10538

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

European-Non Finnish (NFE) AF: 0.288 AC: 19554 AN: 67908

Other (OTH) AF: 0.300 AC: 633 AN: 2108

Alfa AF: 0.256 Hom.: 1535

Bravo AF: 0.327

Asia WGS AF: 0.483 AC: 1678 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	-0.90
CADD	Benign	0.78
DANN	Benign	0.32
PhyloP100		-0.81
PromoterAI		0.051	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: rs758097; hg19: chr19-57742703; COSMIC: COSV57136784; COSMIC: COSV57136784;