NM_198437.3:c.-5-45G>C

Variant names:

• chr20-56388247-C-G
• rs6099126
• NM_198437.3:c.-5-45G>C

Variant summary

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

The NM_198437.3(AURKA):​c.-5-45G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000947 in 1,056,186 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0)
  • Exomes 𝑓: 9.5e-7 (0 hom.)
• Consequence: AURKA NM_198437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• Publications: 0 publications found

Genes affected

AURKA (HGNC:11393): (aurora kinase A) The protein encoded by this gene is a cell cycle-regulated kinase that appears to be involved in microtubule formation and/or stabilization at the spindle pole during chromosome segregation. The encoded protein is found at the centrosome in interphase cells and at the spindle poles in mitosis. This gene may play a role in tumor development and progression. A processed pseudogene of this gene has been found on chromosome 1, and an unprocessed pseudogene has been found on chromosome 10. Multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

AURKA Gene-Disease associations (from GenCC):

• breast cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKA	NM_198437.3	c.-5-45G>C		intron_variant	Intron 1 of 8	ENST00000395915.8	NP_940839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKA	ENST00000395915.8	c.-5-45G>C		intron_variant	Intron 1 of 8	1	NM_198437.3	ENSP00000379251.3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 9.47e-7 AC: 1 AN: 1056186 Hom.: 0 Cov.: 25 AF XY: 0.00000193 AC XY: 1 AN XY: 518508

African (AFR) AF: 0.00 AC: 0 AN: 29110

American (AMR) AF: 0.00 AC: 0 AN: 28982

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16352

East Asian (EAS) AF: 0.00 AC: 0 AN: 13050

South Asian (SAS) AF: 0.00 AC: 0 AN: 47004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27724

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4380

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 850552

Other (OTH) AF: 0.0000256 AC: 1 AN: 39032

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		-0.19
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: rs6099126; hg19: chr20-54963303;