chr13-72745172-G-C

Position:

• chr13-72745172-G-C

Variant summary

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

The NM_024808.5(BORA):​c.703G>C​(p.Val235Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 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: 4.06

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=0.15239105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BORA	NM_024808.5	c.703G>C	p.Val235Leu	missense_variant	8/12	ENST00000390667.11	NP_079084.4
BORA	NM_001286746.3	c.703G>C	p.Val235Leu	missense_variant	8/12		NP_001273675.2
BORA	NM_001366664.2	c.550G>C	p.Val184Leu	missense_variant	6/10		NP_001353593.1
BORA	NM_001286747.2	c.493G>C	p.Val165Leu	missense_variant	7/11		NP_001273676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BORA	ENST00000390667.11	c.703G>C	p.Val235Leu	missense_variant	8/12	1	NM_024808.5	ENSP00000375082	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jan 09, 2024

The c.703G>C (p.V235L) alteration is located in exon 8 (coding exon 7) of the BORA gene. This alteration results from a G to C substitution at nucleotide position 703, causing the valine (V) at amino acid position 235 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	0.20
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T;T;.
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.81	T
MutationTaster	Benign	0.60	D;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.2	.;.;N
REVEL	Benign	0.060
Sift	Benign	0.20	.;.;T
Sift4G	Benign	0.28	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.095
MVP		0.37
MPC		0.65
ClinPred		0.92	D
GERP RS		5.0
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr13-73319310;