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11-66056919-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_006842.3(SF3B2):c.631G>C(p.Gly211Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

SF3B2
NM_006842.3 missense

Scores

2
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, SF3B2
BP4
Computational evidence support a benign effect (MetaRNN=0.1680288).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SF3B2NM_006842.3 linkuse as main transcriptc.631G>C p.Gly211Arg missense_variant 6/22 ENST00000322535.11
SF3B2XM_005273726.5 linkuse as main transcriptc.631G>C p.Gly211Arg missense_variant 6/22
SF3B2XM_011544740.4 linkuse as main transcriptc.628G>C p.Gly210Arg missense_variant 6/22
SF3B2XM_017017144.3 linkuse as main transcriptc.628G>C p.Gly210Arg missense_variant 6/22

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SF3B2ENST00000322535.11 linkuse as main transcriptc.631G>C p.Gly211Arg missense_variant 6/221 NM_006842.3 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31

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 GeneticsMar 27, 2023The c.631G>C (p.G211R) alteration is located in exon 6 (coding exon 6) of the SF3B2 gene. This alteration results from a G to C substitution at nucleotide position 631, causing the glycine (G) at amino acid position 211 to be replaced by an arginine (R). 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
Benign
0.31
BayesDel_addAF
Uncertain
0.021
T
BayesDel_noAF
Benign
-0.21
Cadd
Benign
21
Dann
Uncertain
1.0
DEOGEN2
Benign
0.022
T;T;T;.;.
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.20
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.92
D;D;D;D;D
M_CAP
Benign
0.0091
T
MetaRNN
Benign
0.17
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-1.0
N;N;D;D;D
REVEL
Benign
0.22
Sift
Uncertain
0.0020
D;D;D;D;D
Sift4G
Benign
0.098
T;D;T;D;D
Polyphen
0.23
.;B;.;B;.
Vest4
0.54
MutPred
0.41
.;Gain of MoRF binding (P = 0.0252);.;.;.;
MVP
0.37
MPC
0.54
ClinPred
0.40
T
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.065
gMVP
0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65824390; API