NM_006842.3:c.76G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006842.3(SF3B2):c.76G>T(p.Ala26Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00779 in 1,613,678 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0080 ( 74 hom. )

Consequence

SF3B2
NM_006842.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.06

Publications

12 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007796645).

BP6

Variant 11-66052460-G-T is Benign according to our data. Variant chr11-66052460-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 770770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 937 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SF3B2	NM_006842.3 link	c.76G>T	p.Ala26Ser	missense_variant	Exon 1 of 22	ENST00000322535.11	NP_006833.2	Q13435
SF3B2	XM_005273726.5 link	c.76G>T	p.Ala26Ser	missense_variant	Exon 1 of 22		XP_005273783.1
SF3B2	XM_011544740.4 link	c.76G>T	p.Ala26Ser	missense_variant	Exon 1 of 22		XP_011543042.1
SF3B2	XM_017017144.3 link	c.76G>T	p.Ala26Ser	missense_variant	Exon 1 of 22		XP_016872633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SF3B2	ENST00000322535.11 link	c.76G>T	p.Ala26Ser	missense_variant	Exon 1 of 22	1	NM_006842.3	ENSP00000318861.6		Q13435

Frequencies

GnomAD3 genomes

AF:

0.00615

AC:

936

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00732

Gnomad ASJ

AF:

0.0253

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00945

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00657

AC:

1640

AN:

249662

AF XY:

0.00705

show subpopulations

Gnomad AFR exome

AF:

0.00195

Gnomad AMR exome

AF:

0.00330

Gnomad ASJ exome

AF:

0.0267

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00153

Gnomad NFE exome

AF:

0.00952

Gnomad OTH exome

AF:

0.00640

GnomAD4 exome

AF:

0.00796

AC:

11637

AN:

1461334

Hom.:

Cov.:

AF XY:

0.00802

AC XY:

5827

AN XY:

726968

show subpopulations

African (AFR)

AF:

0.00155

AC:

AN:

33464

American (AMR)

AF:

0.00403

AC:

180

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0243

AC:

634

AN:

26118

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39686

South Asian (SAS)

AF:

0.00285

AC:

246

AN:

86244

European-Finnish (FIN)

AF:

0.00143

AC:

AN:

53232

Middle Eastern (MID)

AF:

0.0114

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00890

AC:

9900

AN:

1111842

Other (OTH)

AF:

0.00799

AC:

482

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

695

1391

2086

2782

3477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00615

AC:

937

AN:

152344

Hom.:

Cov.:

AF XY:

0.00592

AC XY:

441

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00144

AC:

AN:

41586

American (AMR)

AF:

0.00731

AC:

112

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0253

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00310

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000847

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00947

AC:

644

AN:

68014

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

127

170

212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00865

Hom.:

Bravo

AF:

0.00631

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00850

AC:

ExAC

AF:

0.00660

AC:

801

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0118

EpiControl

AF:

0.0116

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SF3B2: BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

T;T;T;.;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.018

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.89

D;D;D;D;D

MetaRNN

Benign

0.0078

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

.;N;.;.;.

PhyloP100

3.1

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.10

N;N;N;N;N

REVEL

Benign

0.053

Sift

Uncertain

0.011

D;D;D;D;D

Sift4G

Benign

0.21

T;T;T;T;T

Polyphen

0.10, 0.012

.;B;.;B;.

Vest4

0.33

MVP

0.46

MPC

0.41

ClinPred

0.044

GERP RS

4.2

PromoterAI

-0.12

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.8

Varity_R

0.21

gMVP

0.26

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

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NM_006842.3:c.76G>T

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