19-57231146-G-GC

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BA1

The NM_001015878.2(AURKC):c.-99dupC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,488,986 control chromosomes in the GnomAD database, including 196,064 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.46 ( 16849 hom., cov: 0)

Exomes 𝑓: 0.50 ( 179215 hom. )

Consequence

AURKC
NM_001015878.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -0.0610

Publications

6 publications found

Variant links:

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

AURKC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP6

Variant 19-57231146-G-GC is Benign according to our data. Variant chr19-57231146-G-GC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 330226.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1, Likely_benign=2}.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
AURKC	NM_001015878.2 link	c.-99dupC	5_prime_UTR_variant	Exon 1 of 7	ENST00000302804.12	NP_001015878.1	Q9UQB9-1
AURKC	XM_047439253.1 link	c.-99dupC	5_prime_UTR_variant	Exon 1 of 5		XP_047295209.1
AURKC	NM_001015879.2 link	c.1+36dupC	intron_variant	Intron 1 of 6		NP_001015879.1	Q9UQB9-3
AURKC	NM_003160.3 link	c.-45+31dupC	intron_variant	Intron 1 of 6		NP_003151.2	Q9UQB9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKC	ENST00000302804.12 link	c.-99dupC		5_prime_UTR_variant	Exon 1 of 7	1	NM_001015878.2	ENSP00000302898.6		Q9UQB9-1

Frequencies

GnomAD3 genomes

AF:

0.460

AC:

69547

AN:

151246

Hom.:

16846

Cov.:

show subpopulations

Gnomad AFR

AF:

0.353

Gnomad AMI

AF:

0.652

Gnomad AMR

AF:

0.448

Gnomad ASJ

AF:

0.542

Gnomad EAS

AF:

0.165

Gnomad SAS

AF:

0.483

Gnomad FIN

AF:

0.542

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.528

Gnomad OTH

AF:

0.454

GnomAD2 exomes

AF:

0.373

AC:

46709

AN:

125078

AF XY:

0.385

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.319

Gnomad ASJ exome

AF:

0.462

Gnomad EAS exome

AF:

0.0787

Gnomad FIN exome

AF:

0.515

Gnomad NFE exome

AF:

0.409

Gnomad OTH exome

AF:

0.377

GnomAD4 exome

AF:

0.502

AC:

671249

AN:

1337622

Hom.:

179215

Cov.:

AF XY:

0.503

AC XY:

331967

AN XY:

659638

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.340

AC:

10231

AN:

30124

American (AMR)

AF:

0.427

AC:

14805

AN:

34632

Ashkenazi Jewish (ASJ)

AF:

0.544

AC:

13182

AN:

24238

East Asian (EAS)

AF:

0.151

AC:

5390

AN:

35588

South Asian (SAS)

AF:

0.505

AC:

38835

AN:

76888

European-Finnish (FIN)

AF:

0.548

AC:

26773

AN:

48862

Middle Eastern (MID)

AF:

0.485

AC:

2674

AN:

5512

European-Non Finnish (NFE)

AF:

0.519

AC:

532772

AN:

1025892

Other (OTH)

AF:

0.476

AC:

26587

AN:

55886

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.380

Heterozygous variant carriers

12194

24387

36581

48774

60968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.460

AC:

69567

AN:

151364

Hom.:

16849

Cov.:

AF XY:

0.459

AC XY:

33953

AN XY:

73914

show subpopulations

African (AFR)

AF:

0.353

AC:

14567

AN:

41278

American (AMR)

AF:

0.446

AC:

6795

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.542

AC:

1874

AN:

3458

East Asian (EAS)

AF:

0.165

AC:

834

AN:

5054

South Asian (SAS)

AF:

0.483

AC:

2313

AN:

4792

European-Finnish (FIN)

AF:

0.542

AC:

5676

AN:

10478

Middle Eastern (MID)

AF:

0.479

AC:

140

AN:

292

European-Non Finnish (NFE)

AF:

0.528

AC:

35818

AN:

67780

Other (OTH)

AF:

0.456

AC:

958

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

1724

3447

5171

6894

8618

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.145

Hom.:

606

Asia WGS

AF:

0.339

AC:

1176

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Spermatogenic Failure

Uncertain:1Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

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

PhyloP100

-0.061

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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19-57231146-G-GC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over