13-72755208-AGT-GGG

Variant names:

• chr13-72755208-AGT-GGG
• NM_024808.5:c.1672_1674delAGTinsGGG
• BORA p.Ser558Gly

Variant summary

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

The NM_024808.5(BORA):​c.1672_1674delAGTinsGGG​(p.Ser558Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BORA NM_024808.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.609
• Publications: 0 publications found

Genes affected

BORA (HGNC:24724): (BORA aurora kinase A activator) BORA is an activator of the protein kinase Aurora A (AURKA; MIM 603072), which is required for centrosome maturation, spindle assembly, and asymmetric protein localization during mitosis (Hutterer et al., 2006 [PubMed 16890155]).[supplied by OMIM, Mar 2008]

DIS3 (HGNC:20604): (DIS3 homolog, exosome endoribonuclease and 3'-5' exoribonuclease) Enables 3'-5'-exoribonuclease activity; endonuclease activity; and guanyl-nucleotide exchange factor activity. Involved in CUT catabolic process and rRNA catabolic process. Located in cytosol and nucleoplasm. Part of nuclear exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024808.5. 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
	BORA	NM_024808.5	MANE Select	c.1672_1674delAGTinsGGG	p.Ser558Gly	missense	N/A	NP_079084.4
	DIS3	NM_014953.5	MANE Select	c.*4585_*4587delACTinsCCC		3_prime_UTR	Exon 21 of 21	NP_055768.3
	BORA	NM_001286746.3		c.1672_1674delAGTinsGGG	p.Ser558Gly	missense	N/A	NP_001273675.2	Q6PGQ7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BORA	ENST00000390667.11	TSL:1 MANE Select	c.1672_1674delAGTinsGGG	p.Ser558Gly	missense	N/A	ENSP00000375082.6	Q6PGQ7-1
	BORA	ENST00000613797.4	TSL:1	c.1897_1899delAGTinsGGG	p.Ser633Gly	missense	N/A	ENSP00000479266.1	A0A087WV86
	DIS3	ENST00000377767.9	TSL:1 MANE Select	c.*4585_*4587delACTinsCCC		3_prime_UTR	Exon 21 of 21	ENSP00000366997.4	Q9Y2L1-1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.61

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr13-73329346;