11-66055118-C-G
Position:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_006842.3(SF3B2):āc.301C>Gā(p.Pro101Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000427 in 1,404,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000043 ( 0 hom. )
Consequence
SF3B2
NM_006842.3 missense
NM_006842.3 missense
Scores
1
4
13
Clinical Significance
Conservation
PhyloP100: 3.93
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 -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, SF3B2
BP4
?
Computational evidence support a benign effect (MetaRNN=0.17281833).
BS2
?
High AC in GnomAdExome4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SF3B2 | NM_006842.3 | c.301C>G | p.Pro101Ala | missense_variant | 4/22 | ENST00000322535.11 | |
SF3B2 | XM_005273726.5 | c.301C>G | p.Pro101Ala | missense_variant | 4/22 | ||
SF3B2 | XM_011544740.4 | c.301C>G | p.Pro101Ala | missense_variant | 4/22 | ||
SF3B2 | XM_017017144.3 | c.301C>G | p.Pro101Ala | missense_variant | 4/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SF3B2 | ENST00000322535.11 | c.301C>G | p.Pro101Ala | missense_variant | 4/22 | 1 | NM_006842.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000935 AC: 2AN: 213880Hom.: 0 AF XY: 0.00000867 AC XY: 1AN XY: 115308
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GnomAD4 exome AF: 0.00000427 AC: 6AN: 1404084Hom.: 0 Cov.: 31 AF XY: 0.00000289 AC XY: 2AN XY: 691510
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GnomAD4 genome ? Cov.: 32
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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 | Aug 04, 2023 | The c.301C>G (p.P101A) alteration is located in exon 4 (coding exon 4) of the SF3B2 gene. This alteration results from a C to G substitution at nucleotide position 301, causing the proline (P) at amino acid position 101 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;T;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;D;D;D;D
REVEL
Benign
Sift
Benign
T;T;T;T;T;.
Sift4G
Benign
T;T;D;D;T;D
Polyphen
0.99, 1.0
.;D;.;D;.;.
Vest4
MVP
MPC
1.1
ClinPred
T
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