Variant 11-116748537-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032725.4(BUD13):c.1805C>T(p.Ala602Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

BUD13
NM_032725.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.50

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.804

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BUD13	NM_032725.4 linkuse as main transcript	c.1805C>T	p.Ala602Val	missense_variant	10/10	ENST00000260210.5	NP_116114.1	Q9BRD0-1
BUD13	NM_001159736.2 linkuse as main transcript	c.1403C>T	p.Ala468Val	missense_variant	10/10		NP_001153208.1	Q9BRD0-2
BUD13	XM_011543035.3 linkuse as main transcript	c.1706C>T	p.Ala569Val	missense_variant	10/10		XP_011541337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BUD13	ENST00000260210.5 linkuse as main transcript	c.1805C>T	p.Ala602Val	missense_variant	10/10	1	NM_032725.4	ENSP00000260210.3	Q9BRD0-1
BUD13	ENST00000375445.7 linkuse as main transcript	c.1403C>T	p.Ala468Val	missense_variant	10/10	1		ENSP00000364594.3	Q9BRD0-2
BUD13	ENST00000419189.1 linkuse as main transcript	n.*225C>T		non_coding_transcript_exon_variant	4/4	5		ENSP00000415748.1	H7C462
BUD13	ENST00000419189.1 linkuse as main transcript	n.*225C>T		3_prime_UTR_variant	4/4	5		ENSP00000415748.1	H7C462

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251476

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Sep 01, 2024

The c.1805C>T (p.A602V) alteration is located in exon 10 (coding exon 10) of the BUD13 gene. This alteration results from a C to T substitution at nucleotide position 1805, causing the alanine (A) at amino acid position 602 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

Pathogenic

0.82

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.071

.;T

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.054

MetaRNN

Pathogenic

0.80

D;D

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.9

.;M

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.2

D;D

REVEL

Uncertain

0.52

Sift

Benign

0.052

T;T

Sift4G

Benign

0.13

T;T

Polyphen

1.0

D;D

Vest4

0.77

MutPred

0.65

.;Loss of disorder (P = 0.0631);

MVP

0.57

MPC

0.48

ClinPred

0.78

GERP RS

5.5

Varity_R

0.55

gMVP

0.51

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