Genetic Variant NM_032725.4:c.358C>T (chr11-116763231-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R120H) has been classified as Likely benign.

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

Publications

42 publications found

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 Gene-Disease associations (from GenCC):

progeroid syndrome
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

BUD13 links:

ENSG00000308823 (HGNC:):

ENSG00000308823 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	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
ENSG00000308823	ENST00000836679.1 link	n.434-2019G>A		intron_variant	Intron 2 of 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

GnomAD2 exomes

AF:

0.0641

AC:

12553

AN:

195762

AF XY:

0.0631

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 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

African (AFR)

AF:

0.0109

AC:

343

AN:

31408

American (AMR)

AF:

0.117

AC:

4017

AN:

34450

Ashkenazi Jewish (ASJ)

AF:

0.0481

AC:

1033

AN:

21482

East Asian (EAS)

AF:

0.0600

AC:

2344

AN:

39088

South Asian (SAS)

AF:

0.0414

AC:

3117

AN:

75246

European-Finnish (FIN)

AF:

0.0574

AC:

2920

AN:

50902

Middle Eastern (MID)

AF:

0.0825

AC:

449

AN:

5440

European-Non Finnish (NFE)

AF:

0.0558

AC:

60260

AN:

1079636

Other (OTH)

AF:

0.0558

AC:

3206

AN:

57440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

4023

8046

12070

16093

20116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2280

4560

6840

9120

11400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0494

AC:

7524

AN:

152196

Hom.:

265

Cov.:

AF XY:

0.0508

AC XY:

3778

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.0127

AC:

529

AN:

41520

American (AMR)

AF:

0.101

AC:

1538

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0478

AC:

166

AN:

3470

East Asian (EAS)

AF:

0.0679

AC:

351

AN:

5170

South Asian (SAS)

AF:

0.0471

AC:

227

AN:

4818

European-Finnish (FIN)

AF:

0.0587

AC:

623

AN:

10616

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0568

AC:

3864

AN:

67992

Other (OTH)

AF:

0.0563

AC:

119

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

360

719

1079

1438

1798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0560

Hom.:

934

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

(source)

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

PhyloP100

1.0

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

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over