11-116757212-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1 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. 15/21 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

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 0 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity BUD13_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054961085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BUD13	NM_032725.4	c.1700G>A	p.Ser567Asn	missense_variant	Exon 9 of 10	ENST00000260210.5	NP_116114.1
BUD13	NM_001159736.2	c.1298G>A	p.Ser433Asn	missense_variant	Exon 9 of 10		NP_001153208.1
BUD13	XM_011543035.3	c.1601G>A	p.Ser534Asn	missense_variant	Exon 9 of 10		XP_011541337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BUD13	ENST00000260210.5	c.1700G>A	p.Ser567Asn	missense_variant	Exon 9 of 10	1	NM_032725.4	ENSP00000260210.3
BUD13	ENST00000375445.7	c.1298G>A	p.Ser433Asn	missense_variant	Exon 9 of 10	1		ENSP00000364594.3
BUD13	ENST00000419189.1	n.*120G>A		non_coding_transcript_exon_variant	Exon 3 of 4	5		ENSP00000415748.1
BUD13	ENST00000419189.1	n.*120G>A		3_prime_UTR_variant	Exon 3 of 4	5		ENSP00000415748.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1700G>A (p.S567N) alteration is located in exon 9 (coding exon 9) of the BUD13 gene. This alteration results from a G to A substitution at nucleotide position 1700, causing the serine (S) at amino acid position 567 to be replaced by an asparagine (N). 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	0.076
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;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.055	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.18	.;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.070	N;N
REVEL	Benign	0.042
Sift	Benign	0.28	T;T
Sift4G	Benign	0.40	T;T
Polyphen		0.0	B;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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-116627928;