Menu
GeneBe

11-66058836-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_006842.3(SF3B2):c.973C>T(p.Arg325Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000199 in 1,608,194 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

SF3B2
NM_006842.3 missense

Scores

6
5
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.32
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2
Missense variant where missense usually causes diseases, SF3B2
BS2
High AC in GnomAdExome at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SF3B2NM_006842.3 linkuse as main transcriptc.973C>T p.Arg325Trp missense_variant 10/22 ENST00000322535.11
SF3B2XM_005273726.5 linkuse as main transcriptc.970C>T p.Arg324Trp missense_variant 10/22
SF3B2XM_011544740.4 linkuse as main transcriptc.970C>T p.Arg324Trp missense_variant 10/22
SF3B2XM_017017144.3 linkuse as main transcriptc.967C>T p.Arg323Trp missense_variant 10/22

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SF3B2ENST00000322535.11 linkuse as main transcriptc.973C>T p.Arg325Trp missense_variant 10/221 NM_006842.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152006
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000322
AC:
8
AN:
248112
Hom.:
0
AF XY:
0.0000446
AC XY:
6
AN XY:
134554
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000295
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000110
Gnomad SAS exome
AF:
0.0000994
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000178
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000192
AC:
28
AN:
1456188
Hom.:
0
Cov.:
32
AF XY:
0.0000221
AC XY:
16
AN XY:
724238
show subpopulations
Gnomad4 AFR exome
AF:
0.0000303
Gnomad4 AMR exome
AF:
0.0000228
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000757
Gnomad4 SAS exome
AF:
0.0000700
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.0000500
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152006
Hom.:
0
Cov.:
31
AF XY:
0.0000404
AC XY:
3
AN XY:
74232
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.0000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000530
Hom.:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000494
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 26, 2023The c.973C>T (p.R325W) alteration is located in exon 10 (coding exon 10) of the SF3B2 gene. This alteration results from a C to T substitution at nucleotide position 973, causing the arginine (R) at amino acid position 325 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.74
BayesDel_addAF
Benign
-0.075
T
BayesDel_noAF
Benign
-0.12
Cadd
Pathogenic
32
Dann
Pathogenic
1.0
DEOGEN2
Benign
0.19
T;T;.;.
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.92
D;D;D;D
M_CAP
Benign
0.083
D
MetaRNN
Uncertain
0.43
T;T;T;T
MetaSVM
Benign
-0.29
T
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.82
D
PROVEAN
Pathogenic
-4.4
D;D;D;D
REVEL
Benign
0.18
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
0.45
MVP
0.39
MPC
1.3
ClinPred
0.68
D
GERP RS
5.2
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
2.8
Varity_R
0.48
gMVP
0.39

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

LitVar

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

Other links and lift over

dbSNP: rs202042073; hg19: chr11-65826307; API