11-116757212-C-T

Variant names:

• chr11-116757212-C-T
• NM_032725.4:c.1700G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032725.4(BUD13):​c.1700G>A​(p.Ser567Asn) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S567G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BUD13 NM_032725.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.300
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• progeroid syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000308823 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054961085).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032725.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BUD13	NM_032725.4	MANE Select	c.1700G>A	p.Ser567Asn	missense	Exon 9 of 10	NP_116114.1	Q9BRD0-1
	BUD13	NM_001159736.2		c.1298G>A	p.Ser433Asn	missense	Exon 9 of 10	NP_001153208.1	Q9BRD0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BUD13	ENST00000260210.5	TSL:1 MANE Select	c.1700G>A	p.Ser567Asn	missense	Exon 9 of 10	ENSP00000260210.3	Q9BRD0-1
	BUD13	ENST00000375445.7	TSL:1	c.1298G>A	p.Ser433Asn	missense	Exon 9 of 10	ENSP00000364594.3	Q9BRD0-2
	BUD13	ENST00000911264.1		c.1697G>A	p.Ser566Asn	missense	Exon 9 of 10	ENSP00000581323.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.80
DANN	Benign	0.77
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.18	N
PhyloP100		-0.30
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.042
Sift	Benign	0.28	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.30		Loss of phosphorylation at S567 (P = 0.0064)
MVP		0.17
MPC		0.094
ClinPred		0.10	T
GERP RS		-5.0
Varity_R		0.038
gMVP		0.055
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

hg19: chr11-116627928;