11-116760826-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_032725.4(BUD13):c.1163C>G(p.Ser388Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0107 in 1,614,144 control chromosomes in the GnomAD database, including 133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0087 (18 hom., cov: 32)
  • Exomes 𝑓: 0.011 (115 hom.)
• Consequence: BUD13 NM_032725.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.68

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0069322884).
• BP6: Variant 11-116760826-G-C is Benign according to our data. Variant chr11-116760826-G-C is described in ClinVar as [Benign]. Clinvar id is 773014.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0109 (15871/1461854) while in subpopulation MID AF= 0.0442 (255/5766). AF 95% confidence interval is 0.0398. There are 115 homozygotes in gnomad4_exome. There are 7978 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BUD13	NM_032725.4	c.1163C>G	p.Ser388Cys	missense_variant	5/10	ENST00000260210.5
BUD13	NM_001159736.2	c.761C>G	p.Ser254Cys	missense_variant	5/10
BUD13	XM_011543035.3	c.1064C>G	p.Ser355Cys	missense_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BUD13	ENST00000260210.5	c.1163C>G	p.Ser388Cys	missense_variant	5/10	1	NM_032725.4	P2
BUD13	ENST00000375445.7	c.761C>G	p.Ser254Cys	missense_variant	5/10	1		A2
BUD13	ENST00000419189.1	c.284+1727C>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00878 AC: 1336 AN: 152172 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.00222

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.00798

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.0122

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0124

GnomAD3 exomes AF: 0.00964 AC: 2425 AN: 251490 Hom.: 19 AF XY: 0.0100 AC XY: 1359 AN XY: 135922

Gnomad AFR exome AF: 0.00203

Gnomad AMR exome AF: 0.00543

Gnomad ASJ exome AF: 0.00565

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00438

Gnomad FIN exome AF: 0.0127

Gnomad NFE exome AF: 0.0144

Gnomad OTH exome AF: 0.0158

GnomAD4 exome AF: 0.0109 AC: 15871 AN: 1461854 Hom.: 115 Cov.: 32 AF XY: 0.0110 AC XY: 7978 AN XY: 727234

Gnomad4 AFR exome AF: 0.00278

Gnomad4 AMR exome AF: 0.00550

Gnomad4 ASJ exome AF: 0.00647

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00470

Gnomad4 FIN exome AF: 0.0122

Gnomad4 NFE exome AF: 0.0121

Gnomad4 OTH exome AF: 0.0103

GnomAD4 genome AF: 0.00875 AC: 1332 AN: 152290 Hom.: 18 Cov.: 32 AF XY: 0.00865 AC XY: 644 AN XY: 74472

Gnomad4 AFR AF: 0.00219

Gnomad4 AMR AF: 0.00797

Gnomad4 ASJ AF: 0.00691

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00540

Gnomad4 FIN AF: 0.0122

Gnomad4 NFE AF: 0.0123

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0108 Hom.: 6

Bravo AF: 0.00836

TwinsUK AF: 0.0111 AC: 41

ALSPAC AF: 0.0101 AC: 39

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.0159 AC: 137

ExAC AF: 0.00995 AC: 1208

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0169

EpiControl AF: 0.0154

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.29
Cadd	Pathogenic	27
Dann	Uncertain	0.99
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D
MetaRNN	Benign	0.0069	T;T
MetaSVM	Benign	-0.80	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		1.0	D;D
Vest4		0.37
MVP		0.66
MPC		0.46
ClinPred		0.050	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs35004487; hg19: chr11-116631542; COSMIC: COSV99036345;