rs145088115

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006842.3(SF3B2):c.401G>A(p.Arg134His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,612,356 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R134P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00040 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

SF3B2
NM_006842.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.27

Publications

0 publications found

Variant links:

Genes affected

SF3B2 (HGNC:10769): (splicing factor 3b subunit 2) This gene encodes subunit 2 of the splicing factor 3b protein complex. Splicing factor 3b, together with splicing factor 3a and a 12S RNA unit, forms the U2 small nuclear ribonucleoproteins complex (U2 snRNP). The splicing factor 3b/3a complex binds pre-mRNA upstream of the intron's branch site in a sequence-independent manner and may anchor the U2 snRNP to the pre-mRNA. Splicing factor 3b is also a component of the minor U12-type spliceosome. Subunit 2 associates with pre-mRNA upstream of the branch site at the anchoring site. Subunit 2 also interacts directly with subunit 4 of the splicing factor 3b complex. Subunit 2 is a highly hydrophilic protein with a proline-rich N-terminus and a glutamate-rich stretch in the C-terminus. [provided by RefSeq, Jul 2008]

SF3B2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0106675625).

BP6

Variant 11-66055218-G-A is Benign according to our data. Variant chr11-66055218-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3794761.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 61 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SF3B2	NM_006842.3 link	c.401G>A	p.Arg134His	missense_variant	Exon 4 of 22	ENST00000322535.11	NP_006833.2	Q13435
SF3B2	XM_005273726.5 link	c.401G>A	p.Arg134His	missense_variant	Exon 4 of 22		XP_005273783.1
SF3B2	XM_011544740.4 link	c.401G>A	p.Arg134His	missense_variant	Exon 4 of 22		XP_011543042.1
SF3B2	XM_017017144.3 link	c.401G>A	p.Arg134His	missense_variant	Exon 4 of 22		XP_016872633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SF3B2	ENST00000322535.11 link	c.401G>A	p.Arg134His	missense_variant	Exon 4 of 22	1	NM_006842.3	ENSP00000318861.6		Q13435

Frequencies

GnomAD3 genomes

AF:

0.000402

AC:

AN:

151852

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000232

AC:

AN:

249764

AF XY:

0.000200

show subpopulations

Gnomad AFR exome

AF:

0.00205

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000445

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000726

AC:

106

AN:

1460386

Hom.:

Cov.:

AF XY:

0.0000730

AC XY:

AN XY:

726440

show subpopulations

African (AFR)

AF:

0.00164

AC:

AN:

33440

American (AMR)

AF:

0.000425

AC:

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39642

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53208

Middle Eastern (MID)

AF:

0.000348

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000252

AC:

AN:

1111056

Other (OTH)

AF:

0.0000166

AC:

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000401

AC:

AN:

151970

Hom.:

Cov.:

AF XY:

0.000431

AC XY:

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.00120

AC:

AN:

41512

American (AMR)

AF:

0.000654

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000195

AC:

AN:

5128

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67966

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000161

Hom.:

Bravo

AF:

0.000502

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000255

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Feb 20, 2025

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0084

T;T;T;.;.;T

Eigen

Benign

0.092

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.86

D;D;D;D;D;D

M_CAP

Benign

0.0033

MetaRNN

Benign

0.011

T;T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.58

.;N;.;.;.;.

PhyloP100

1.3

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.080

N;N;N;N;N;D

REVEL

Benign

0.069

Sift

Benign

0.065

T;D;T;T;T;.

Sift4G

Benign

0.16

T;T;T;T;T;T

Polyphen

0.97, 1.0

.;D;.;D;.;.

Vest4

0.15

MVP

0.26

MPC

1.4

ClinPred

0.028

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.027

gMVP

0.079

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs145088115

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over