Variant 11-116757915-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032725.4(BUD13):c.1535A>T(p.Glu512Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000164 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

BUD13
NM_032725.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.33

Variant links:

Genes affected

BUD13 (HGNC:28199): (BUD13 homolog) Enables RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in nucleoplasm. Part of U2-type precatalytic spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

BUD13 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BUD13	NM_032725.4 linkuse as main transcript	c.1535A>T	p.Glu512Val	missense_variant	8/10	ENST00000260210.5	NP_116114.1
BUD13	NM_001159736.2 linkuse as main transcript	c.1133A>T	p.Glu378Val	missense_variant	8/10		NP_001153208.1
BUD13	XM_011543035.3 linkuse as main transcript	c.1436A>T	p.Glu479Val	missense_variant	8/10		XP_011541337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BUD13	ENST00000260210.5 linkuse as main transcript	c.1535A>T	p.Glu512Val	missense_variant	8/10	1	NM_032725.4	ENSP00000260210	P2	Q9BRD0-1
BUD13	ENST00000375445.7 linkuse as main transcript	c.1133A>T	p.Glu378Val	missense_variant	8/10	1		ENSP00000364594	A2	Q9BRD0-2
BUD13	ENST00000419189.1 linkuse as main transcript	c.312A>T	p.Gly104=	synonymous_variant, NMD_transcript_variant	2/4	5		ENSP00000415748

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461844

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727218

show subpopulations

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:

0.0000216

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2023

The c.1535A>T (p.E512V) alteration is located in exon 8 (coding exon 8) of the BUD13 gene. This alteration results from a A to T substitution at nucleotide position 1535, causing the glutamic acid (E) at amino acid position 512 to be replaced by a valine (V). 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

0.27

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.045

.;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.51

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Benign

0.17

Sift

Benign

0.11

T;T

Sift4G

Benign

0.065

T;T

Polyphen

0.75

P;P

Vest4

0.57

MutPred

0.50

.;Gain of MoRF binding (P = 0.0328);

MVP

0.42

MPC

0.48

ClinPred

0.95

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.45

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over