chr13-72746639-T-C

Position:

• chr13-72746639-T-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.1010T>C​(p.Met337Thr) 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. 14/19 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: 0.827

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=0.088903874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BORA	NM_024808.5	c.1010T>C	p.Met337Thr	missense_variant	10/12	ENST00000390667.11
BORA	NM_001286746.3	c.1010T>C	p.Met337Thr	missense_variant	10/12
BORA	NM_001366664.2	c.857T>C	p.Met286Thr	missense_variant	8/10
BORA	NM_001286747.2	c.800T>C	p.Met267Thr	missense_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BORA	ENST00000390667.11	c.1010T>C	p.Met337Thr	missense_variant	10/12	1	NM_024808.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.00000756

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

Sep 30, 2021

The c.1010T>C (p.M337T) alteration is located in exon 10 (coding exon 9) of the BORA gene. This alteration results from a T to C substitution at nucleotide position 1010, causing the methionine (M) at amino acid position 337 to be replaced by a threonine (T). 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	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.4
DANN	Benign	0.33
DEOGEN2	Benign	0.012	T;T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.54	T;T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.089	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.28	.;.;N
REVEL	Benign	0.032
Sift	Benign	0.63	.;.;T
Sift4G	Benign	0.84	T;T;T
Polyphen		0.0020	B;.;.
Vest4		0.062
MVP		0.23
MPC		0.27
ClinPred		0.030	T
GERP RS		0.15
gMVP		0.20

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

Publications

LitVar

Other links and lift over

dbSNP: rs922959716; hg19: chr13-73320777;