13-72731320-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024808.5(BORA):c.193G>A(p.Val65Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BORA NM_024808.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.34

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0878512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BORA	NM_024808.5	c.193G>A	p.Val65Ile	missense_variant	3/12	ENST00000390667.11
BORA	NM_001286746.3	c.193G>A	p.Val65Ile	missense_variant	3/12
BORA	NM_001286747.2	c.50+2227G>A		intron_variant
BORA	NM_001366664.2	c.153+2227G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BORA	ENST00000390667.11	c.193G>A	p.Val65Ile	missense_variant	3/12	1	NM_024808.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460012 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726392

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 04, 2023

The c.193G>A (p.V65I) alteration is located in exon 3 (coding exon 2) of the BORA gene. This alteration results from a G to A substitution at nucleotide position 193, causing the valine (V) at amino acid position 65 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
Cadd	Benign	17
Dann	Benign	0.95
DEOGEN2	Benign	0.014	T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.088	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.33	T
REVEL	Benign	0.030
Sift4G	Benign	0.52	T;T
Vest4		0.14
MVP		0.48
MPC		0.19
ClinPred		0.25	T
GERP RS		4.6
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-73305458;