chr17-8206624-C-G

Variant names:

• chr17-8206624-C-G
• rs993921967
• NM_004217.4:c.553G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004217.4(AURKB):​c.553G>C​(p.Ala185Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A185S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AURKB NM_004217.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.11
• Publications: 0 publications found

Genes affected

AURKB (HGNC:11390): (aurora kinase B) This gene encodes a member of the aurora kinase subfamily of serine/threonine kinases. The genes encoding the other two members of this subfamily are located on chromosomes 19 and 20. These kinases participate in the regulation of alignment and segregation of chromosomes during mitosis and meiosis through association with microtubules. A pseudogene of this gene is located on chromosome 8. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.87

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004217.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKB	NM_004217.4	MANE Select	c.553G>C	p.Ala185Pro	missense	Exon 7 of 9	NP_004208.2	Q96GD4-1
	AURKB	NM_001284526.2		c.556G>C	p.Ala186Pro	missense	Exon 7 of 9	NP_001271455.1	Q96GD4-5
	AURKB	NM_001313950.2		c.553G>C	p.Ala185Pro	missense	Exon 7 of 9	NP_001300879.1	Q96GD4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKB	ENST00000585124.6	TSL:1 MANE Select	c.553G>C	p.Ala185Pro	missense	Exon 7 of 9	ENSP00000463999.1	Q96GD4-1
	AURKB	ENST00000316199.10	TSL:1	c.556G>C	p.Ala186Pro	missense	Exon 7 of 9	ENSP00000313950.6	Q96GD4-5
	AURKB	ENST00000578549.5	TSL:1	c.457G>C	p.Ala153Pro	missense	Exon 6 of 8	ENSP00000462207.1	Q96GD4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.025	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		4.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.78		Loss of stability (P = 0.0859)
MVP		0.78
MPC		0.89
ClinPred		0.99	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.96
gMVP		0.87

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: rs993921967; hg19: chr17-8109942;