11-116757915-T-A

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.33

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]

ACMG classification

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	UniProt
BUD13	NM_032725.4	c.1535A>T	p.Glu512Val	missense_variant	8/10	ENST00000260210.5
BUD13	NM_001159736.2	c.1133A>T	p.Glu378Val	missense_variant	8/10
BUD13	XM_011543035.3	c.1436A>T	p.Glu479Val	missense_variant	8/10

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461844 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 727218

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.: 32

Bravo AF: 0.00000378

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

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

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	T
BayesDel_noAF	Benign	-0.30
Cadd	Pathogenic	28
Dann	Uncertain	0.99
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.55	T
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	D
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

Other links and lift over

dbSNP: rs754863712; hg19: chr11-116628631;