19-57231121-C-T

Position:

chr19-57231121-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000302804.12(AURKC):c.-128C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 151,514 control chromosomes in the GnomAD database, including 44,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 44871 hom., cov: 29)

Exomes 𝑓: 0.83 ( 464805 hom. )

Failed GnomAD Quality Control

Consequence

AURKC
ENST00000302804.12 5_prime_UTR

Scores

Splicing: ADA: 0.00001267

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.12

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 19-57231121-C-T is Benign according to our data. Variant chr19-57231121-C-T is described in ClinVar as [Benign]. Clinvar id is 330225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-57231121-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
AURKC	NM_001015878.2 linkuse as main transcript	c.-128C>T	5_prime_UTR_variant	1/7	ENST00000302804.12	NP_001015878.1
AURKC	NM_003160.3 linkuse as main transcript	c.-45+2C>T	splice_donor_variant			NP_003151.2
AURKC	XM_047439253.1 linkuse as main transcript	c.-128C>T	5_prime_UTR_variant	1/5		XP_047295209.1
AURKC	NM_001015879.2 linkuse as main transcript	c.1+7C>T	splice_region_variant, intron_variant			NP_001015879.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AURKC	ENST00000302804.12 linkuse as main transcript	c.-128C>T	5_prime_UTR_variant	1/7	1	NM_001015878.2	ENSP00000302898	A2	Q9UQB9-1
AURKC	ENST00000415300.6 linkuse as main transcript	c.1+7C>T	splice_region_variant, intron_variant		1		ENSP00000407162		Q9UQB9-3
AURKC	ENST00000601799.5 linkuse as main transcript		upstream_gene_variant		3		ENSP00000468918

Frequencies

GnomAD3 genomes

AF:

0.762

AC:

115396

AN:

151398

Hom.:

44862

Cov.:

show subpopulations

Gnomad AFR

AF:

0.597

Gnomad AMI

AF:

0.804

Gnomad AMR

AF:

0.793

Gnomad ASJ

AF:

0.854

Gnomad EAS

AF:

0.848

Gnomad SAS

AF:

0.852

Gnomad FIN

AF:

0.906

Gnomad MID

AF:

0.736

Gnomad NFE

AF:

0.816

Gnomad OTH

AF:

0.745

GnomAD3 exomes

AF:

0.828

AC:

108806

AN:

131394

Hom.:

50752

AF XY:

0.836

AC XY:

57932

AN XY:

69338

show subpopulations

Gnomad AFR exome

AF:

0.563

Gnomad AMR exome

AF:

0.843

Gnomad ASJ exome

AF:

0.857

Gnomad EAS exome

AF:

0.854

Gnomad SAS exome

AF:

0.873

Gnomad FIN exome

AF:

0.925

Gnomad NFE exome

AF:

0.806

Gnomad OTH exome

AF:

0.800

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.831

AC:

1100918

AN:

1325072

Hom.:

464805

Cov.:

AF XY:

0.833

AC XY:

543735

AN XY:

652370

show subpopulations

Gnomad4 AFR exome

AF:

0.596

Gnomad4 AMR exome

AF:

0.847

Gnomad4 ASJ exome

AF:

0.868

Gnomad4 EAS exome

AF:

0.841

Gnomad4 SAS exome

AF:

0.876

Gnomad4 FIN exome

AF:

0.901

Gnomad4 NFE exome

AF:

0.830

Gnomad4 OTH exome

AF:

0.817

GnomAD4 genome

AF:

0.762

AC:

115443

AN:

151514

Hom.:

44871

Cov.:

AF XY:

0.768

AC XY:

56844

AN XY:

74014

show subpopulations

Gnomad4 AFR

AF:

0.597

Gnomad4 AMR

AF:

0.793

Gnomad4 ASJ

AF:

0.854

Gnomad4 EAS

AF:

0.848

Gnomad4 SAS

AF:

0.850

Gnomad4 FIN

AF:

0.906

Gnomad4 NFE

AF:

0.816

Gnomad4 OTH

AF:

0.744

Alfa

AF:

0.787

Hom.:

10254

Bravo

AF:

0.748

Asia WGS

AF:

0.805

AC:

2796

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 1655/2178=75.9% -

Infertility associated with multi-tailed spermatozoa and excessive DNA

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.9

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000013

dbscSNV1_RF

Benign

0.022

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over