13-72753786-G-C

Position:

• chr13-72753786-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.1579G>C​(p.Glu527Gln) 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: 2.24

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]

DIS3 (HGNC:20604): (DIS3 homolog, exosome endoribonuclease and 3'-5' exoribonuclease) Enables 3'-5'-exoribonuclease activity; endonuclease activity; and guanyl-nucleotide exchange factor activity. Involved in CUT catabolic process and rRNA catabolic process. Located in cytosol and nucleoplasm. Part of nuclear exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]

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=0.20372373).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BORA	NM_024808.5	c.1579G>C	p.Glu527Gln	missense_variant	11/12	ENST00000390667.11	NP_079084.4
DIS3	NM_014953.5	c.*6009C>G		3_prime_UTR_variant	21/21	ENST00000377767.9	NP_055768.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BORA	ENST00000390667.11	c.1579G>C	p.Glu527Gln	missense_variant	11/12	1	NM_024808.5	ENSP00000375082.6
DIS3	ENST00000377767	c.*6009C>G		3_prime_UTR_variant	21/21	1	NM_014953.5	ENSP00000366997.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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 08, 2022

The c.1579G>C (p.E527Q) alteration is located in exon 11 (coding exon 10) of the BORA gene. This alteration results from a G to C substitution at nucleotide position 1579, causing the glutamic acid (E) at amino acid position 527 to be replaced by a glutamine (Q). 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	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	T;T;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.82	T
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.95	.;.;N
REVEL	Benign	0.14
Sift	Uncertain	0.016	.;.;D
Sift4G	Benign	0.20	T;T;D
Polyphen		1.0	D;.;.
Vest4		0.30
MVP		0.45
MPC		0.48
ClinPred		0.54	D
GERP RS		3.8
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr13-73327924;