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11-66057328-C-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_ModerateBP6_ModerateBS2

The NM_006842.3(SF3B2):c.730C>G(p.Pro244Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 1,605,730 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000092 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

SF3B2
NM_006842.3 missense

Scores

4
14

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.08
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP2
Missense variant where missense usually causes diseases, SF3B2
BP4
Computational evidence support a benign effect (MetaRNN=0.12541696).
BP6
Variant 11-66057328-C-G is Benign according to our data. Variant chr11-66057328-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3160822.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SF3B2NM_006842.3 linkuse as main transcriptc.730C>G p.Pro244Ala missense_variant 7/22 ENST00000322535.11
SF3B2XM_005273726.5 linkuse as main transcriptc.727C>G p.Pro243Ala missense_variant 7/22
SF3B2XM_011544740.4 linkuse as main transcriptc.727C>G p.Pro243Ala missense_variant 7/22
SF3B2XM_017017144.3 linkuse as main transcriptc.724C>G p.Pro242Ala missense_variant 7/22

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SF3B2ENST00000322535.11 linkuse as main transcriptc.730C>G p.Pro244Ala missense_variant 7/221 NM_006842.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152190
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000176
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000180
AC:
45
AN:
249894
Hom.:
0
AF XY:
0.000199
AC XY:
27
AN XY:
135718
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000380
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.000283
AC:
412
AN:
1453540
Hom.:
0
Cov.:
29
AF XY:
0.000289
AC XY:
209
AN XY:
723664
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000353
Gnomad4 OTH exome
AF:
0.000316
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152190
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000219
Hom.:
0
Bravo
AF:
0.000132
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000214
AC:
26
EpiCase
AF:
0.000382
EpiControl
AF:
0.000119

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsDec 13, 2023This 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
0.058
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.40
Cadd
Benign
19
Dann
Uncertain
0.98
DEOGEN2
Benign
0.026
T;T;T;.;.
Eigen
Benign
0.0036
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.75
T;T;T;T;T
M_CAP
Benign
0.0034
T
MetaRNN
Benign
0.13
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
0.87
N;N
PrimateAI
Uncertain
0.79
T
PROVEAN
Benign
-1.8
N;N;D;D;D
REVEL
Benign
0.032
Sift
Benign
0.046
D;T;T;T;T
Sift4G
Uncertain
0.021
D;D;D;D;D
Polyphen
0.30
.;B;.;.;.
Vest4
0.28
MVP
0.32
MPC
0.44
ClinPred
0.070
T
GERP RS
5.3
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.8
Varity_R
0.031
gMVP
0.14

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: rs201649157; hg19: chr11-65824799; API