dbSNP rs10488698: BUD13:p.Arg120Cys (chr11-116763231-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032725.4(BUD13):c.358C>T(p.Arg120Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 1,547,288 control chromosomes in the GnomAD database, including 2,639 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.049 ( 265 hom., cov: 32)

Exomes 𝑓: 0.056 ( 2374 hom. )

Consequence

BUD13
NM_032725.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.01

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017531514).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BUD13	NM_032725.4 link	c.358C>T	p.Arg120Cys	missense_variant	Exon 4 of 10	ENST00000260210.5	NP_116114.1	Q9BRD0-1
BUD13	NM_001159736.2 link	c.358C>T	p.Arg120Cys	missense_variant	Exon 4 of 10		NP_001153208.1	Q9BRD0-2
BUD13	XM_011543035.3 link	c.259C>T	p.Arg87Cys	missense_variant	Exon 4 of 10		XP_011541337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BUD13	ENST00000260210.5 link	c.358C>T	p.Arg120Cys	missense_variant	Exon 4 of 10	1	NM_032725.4	ENSP00000260210.3		Q9BRD0-1
BUD13	ENST00000375445.7 link	c.358C>T	p.Arg120Cys	missense_variant	Exon 4 of 10	1		ENSP00000364594.3		Q9BRD0-2

Frequencies

GnomAD3 genomes

AF:

0.0495

AC:

7532

AN:

152078

Hom.:

265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0128

Gnomad AMI

AF:

0.0934

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.0478

Gnomad EAS

AF:

0.0681

Gnomad SAS

AF:

0.0473

Gnomad FIN

AF:

0.0587

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0568

Gnomad OTH

AF:

0.0579

GnomAD3 exomes

AF:

0.0641

AC:

12553

AN:

195762

Hom.:

492

AF XY:

0.0631

AC XY:

6581

AN XY:

104236

show subpopulations

Gnomad AFR exome

AF:

0.0115

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.0391

Gnomad EAS exome

AF:

0.0743

Gnomad SAS exome

AF:

0.0416

Gnomad FIN exome

AF:

0.0598

Gnomad NFE exome

AF:

0.0614

Gnomad OTH exome

AF:

0.0658

GnomAD4 exome

AF:

0.0557

AC:

77689

AN:

1395092

Hom.:

2374

Cov.:

AF XY:

0.0556

AC XY:

38154

AN XY:

686682

show subpopulations

Gnomad4 AFR exome

AF:

0.0109

Gnomad4 AMR exome

AF:

0.117

Gnomad4 ASJ exome

AF:

0.0481

Gnomad4 EAS exome

AF:

0.0600

Gnomad4 SAS exome

AF:

0.0414

Gnomad4 FIN exome

AF:

0.0574

Gnomad4 NFE exome

AF:

0.0558

Gnomad4 OTH exome

AF:

0.0558

GnomAD4 genome

AF:

0.0494

AC:

7524

AN:

152196

Hom.:

265

Cov.:

AF XY:

0.0508

AC XY:

3778

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0127

Gnomad4 AMR

AF:

0.101

Gnomad4 ASJ

AF:

0.0478

Gnomad4 EAS

AF:

0.0679

Gnomad4 SAS

AF:

0.0471

Gnomad4 FIN

AF:

0.0587

Gnomad4 NFE

AF:

0.0568

Gnomad4 OTH

AF:

0.0563

Alfa

AF:

0.0576

Hom.:

654

Bravo

AF:

0.0525

TwinsUK

AF:

0.0537

AC:

199

ALSPAC

AF:

0.0545

AC:

210

ESP6500AA

AF:

0.0114

AC:

ESP6500EA

AF:

0.0541

AC:

465

ExAC

AF:

0.0607

AC:

7347

Asia WGS

AF:

0.0680

AC:

235

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.0085

.;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.80

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-3.7

D;D

REVEL

Benign

0.12

Sift

Benign

0.14

T;T

Sift4G

Uncertain

0.044

D;T

Polyphen

0.0020

B;B

Vest4

0.12

MPC

0.13

ClinPred

0.011

GERP RS

3.9

Varity_R

0.074

gMVP

0.079

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over