chr13-72746735-C-T

Position:

• chr13-72746735-C-T

Variant summary

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

The NM_024808.5(BORA):​c.1106C>T​(p.Pro369Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 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)
• Consequence: BORA NM_024808.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.686

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=0.091625154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BORA	NM_024808.5	c.1106C>T	p.Pro369Leu	missense_variant	10/12	ENST00000390667.11	NP_079084.4
BORA	NM_001286746.3	c.1106C>T	p.Pro369Leu	missense_variant	10/12		NP_001273675.2
BORA	NM_001366664.2	c.953C>T	p.Pro318Leu	missense_variant	8/10		NP_001353593.1
BORA	NM_001286747.2	c.896C>T	p.Pro299Leu	missense_variant	9/11		NP_001273676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BORA	ENST00000390667.11	c.1106C>T	p.Pro369Leu	missense_variant	10/12	1	NM_024808.5	ENSP00000375082	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Feb 17, 2024

The c.1106C>T (p.P369L) alteration is located in exon 10 (coding exon 9) of the BORA gene. This alteration results from a C to T substitution at nucleotide position 1106, causing the proline (P) at amino acid position 369 to be replaced by a leucine (L). 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	0.068
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.038	T;T;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.092	T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.6	.;.;D
REVEL	Benign	0.067
Sift	Benign	0.032	.;.;D
Sift4G	Benign	0.085	T;T;T
Polyphen		0.010	B;.;.
Vest4		0.029
MVP		0.26
MPC		0.26
ClinPred		0.18	T
GERP RS		3.1
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2033154867; hg19: chr13-73320873;