11-116758312-T-C

Position:

• chr11-116758312-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032725.4(BUD13):​c.1456A>G​(p.Lys486Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 6.8e-7 (0 hom.)
• Consequence: BUD13 NM_032725.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.17

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05981946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BUD13	NM_032725.4	c.1456A>G	p.Lys486Glu	missense_variant	7/10	ENST00000260210.5
BUD13	NM_001159736.2	c.1054A>G	p.Lys352Glu	missense_variant	7/10
BUD13	XM_011543035.3	c.1357A>G	p.Lys453Glu	missense_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BUD13	ENST00000260210.5	c.1456A>G	p.Lys486Glu	missense_variant	7/10	1	NM_032725.4	P2
BUD13	ENST00000375445.7	c.1054A>G	p.Lys352Glu	missense_variant	7/10	1		A2
BUD13	ENST00000419189.1	c.285-372A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

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

Aug 12, 2021

The c.1456A>G (p.K486E) alteration is located in exon 7 (coding exon 7) of the BUD13 gene. This alteration results from a A to G substitution at nucleotide position 1456, causing the lysine (K) at amino acid position 486 to be replaced by a glutamic acid (E). 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	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.031
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.11
Sift	Benign	0.35	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.0010	B;B
Vest4		0.19
MutPred		0.46		.;Loss of ubiquitination at K486 (P = 0.0022);
MVP		0.33
MPC		0.19
ClinPred		0.55	D
GERP RS		4.3
Varity_R		0.15
gMVP		0.074

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr11-116629028;