11-66058836-C-T
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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
NM_006842.3 missense
Scores
6
5
7
Clinical Significance
Conservation
PhyloP100: 5.32
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 Likely_benign. Variant got -3 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, SF3B2
BS2
?
High AC in GnomAdExome4 at 28 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SF3B2 | NM_006842.3 | c.973C>T | p.Arg325Trp | missense_variant | 10/22 | ENST00000322535.11 | |
SF3B2 | XM_005273726.5 | c.970C>T | p.Arg324Trp | missense_variant | 10/22 | ||
SF3B2 | XM_011544740.4 | c.970C>T | p.Arg324Trp | missense_variant | 10/22 | ||
SF3B2 | XM_017017144.3 | c.967C>T | p.Arg323Trp | missense_variant | 10/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SF3B2 | ENST00000322535.11 | c.973C>T | p.Arg325Trp | missense_variant | 10/22 | 1 | NM_006842.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152006Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000322 AC: 8AN: 248112Hom.: 0 AF XY: 0.0000446 AC XY: 6AN XY: 134554
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GnomAD4 exome AF: 0.0000192 AC: 28AN: 1456188Hom.: 0 Cov.: 32 AF XY: 0.0000221 AC XY: 16AN XY: 724238
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152006Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3AN XY: 74232
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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 submitter | clinical testing | Ambry Genetics | Sep 26, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
MVP
MPC
1.3
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at