20-56369904-A-G

Variant names:

• chr20-56369904-A-G
• rs6099119
• NM_198437.3:c.*254T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_198437.3(AURKA):​c.*254T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00429 in 571,954 control chromosomes in the GnomAD database, including 39 homozygotes. 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: 𝑓 0.012 (27 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (12 hom.)
• Consequence: AURKA NM_198437.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0116 (1768/152326) while in subpopulation AFR AF = 0.04 (1665/41574). AF 95% confidence interval is 0.0384. There are 27 homozygotes in GnomAd4. There are 823 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1768 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198437.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKA	NM_198437.3	MANE Select	c.*254T>C		3_prime_UTR	Exon 9 of 9	NP_940839.1
	AURKA	NM_001424418.1		c.*254T>C		3_prime_UTR	Exon 11 of 11	NP_001411347.1
	AURKA	NM_001424419.1		c.*254T>C		3_prime_UTR	Exon 11 of 11	NP_001411348.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKA	ENST00000395915.8	TSL:1 MANE Select	c.*254T>C		3_prime_UTR	Exon 9 of 9	ENSP00000379251.3
	AURKA	ENST00000312783.10	TSL:1	c.*254T>C		3_prime_UTR	Exon 10 of 10	ENSP00000321591.6
	AURKA	ENST00000347343.6	TSL:1	c.*254T>C		3_prime_UTR	Exon 9 of 9	ENSP00000216911.2

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1754 AN: 152208 Hom.: 26 Cov.: 33

Gnomad AFR AF: 0.0398

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00717

GnomAD4 exome AF: 0.00163 AC: 685 AN: 419628 Hom.: 12 Cov.: 4 AF XY: 0.00140 AC XY: 311 AN XY: 222638

African (AFR) AF: 0.0395 AC: 489 AN: 12370

American (AMR) AF: 0.00316 AC: 68 AN: 21550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13324

East Asian (EAS) AF: 0.00 AC: 0 AN: 27140

South Asian (SAS) AF: 0.000106 AC: 5 AN: 47372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22824

Middle Eastern (MID) AF: 0.000560 AC: 1 AN: 1786

European-Non Finnish (NFE) AF: 0.000237 AC: 59 AN: 249410

Other (OTH) AF: 0.00264 AC: 63 AN: 23852

GnomAD4 genome AF: 0.0116 AC: 1768 AN: 152326 Hom.: 27 Cov.: 33 AF XY: 0.0110 AC XY: 823 AN XY: 74490

African (AFR) AF: 0.0400 AC: 1665 AN: 41574

American (AMR) AF: 0.00444 AC: 68 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68024

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.00456 Hom.: 9

Bravo AF: 0.0133

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.59
PhyloP100		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs6099119; hg19: chr20-54944960;