chr13-72731372-A-T

Position:

• chr13-72731372-A-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.245A>T​(p.Tyr82Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000756 in 1,455,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 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: 0.0000076 (0 hom.)
• Consequence: BORA NM_024808.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.88

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=0.16071731).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BORA	NM_024808.5	c.245A>T	p.Tyr82Phe	missense_variant	3/12	ENST00000390667.11
BORA	NM_001286746.3	c.245A>T	p.Tyr82Phe	missense_variant	3/12
BORA	NM_001286747.2	c.50+2279A>T		intron_variant
BORA	NM_001366664.2	c.153+2279A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BORA	ENST00000390667.11	c.245A>T	p.Tyr82Phe	missense_variant	3/12	1	NM_024808.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000756 AC: 11 AN: 1455362 Hom.: 0 Cov.: 29 AF XY: 0.00000414 AC XY: 3 AN XY: 724376

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: 0.00000994

Gnomad4 OTH exome AF: 0.00

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

Jul 08, 2022

The c.245A>T (p.Y82F) alteration is located in exon 3 (coding exon 2) of the BORA gene. This alteration results from a A to T substitution at nucleotide position 245, causing the tyrosine (Y) at amino acid position 82 to be replaced by a phenylalanine (F). 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	0.13
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.061	T;T
Eigen	Benign	-0.095
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.85	T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.73	D;D
PrimateAI	Uncertain	0.54	T
REVEL	Benign	0.074
Sift4G	Benign	0.21	T;T
Vest4		0.35
MVP		0.39
MPC		0.28
ClinPred		0.53	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.49

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: rs2032812645; hg19: chr13-73305510;