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GeneBe

16-70529158-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate

The NM_012426.5(SF3B3):c.356A>G(p.Gln119Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SF3B3
NM_012426.5 missense

Scores

12
4
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.31
Variant links:
Genes affected
SF3B3 (HGNC:10770): (splicing factor 3b subunit 3) This gene encodes subunit 3 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 3 has also been identified as a component of the STAGA (SPT3-TAF(II)31-GCN5L acetylase) transcription coactivator-HAT (histone acetyltransferase) complex, and the TFTC (TATA-binding-protein-free TAF(II)-containing complex). These complexes may function in chromatin modification, transcription, splicing, and DNA repair. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, SF3B3
PP3
MetaRNN computational evidence supports a deleterious effect, 0.843

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SF3B3NM_012426.5 linkuse as main transcriptc.356A>G p.Gln119Arg missense_variant 3/26 ENST00000302516.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SF3B3ENST00000302516.10 linkuse as main transcriptc.356A>G p.Gln119Arg missense_variant 3/261 NM_012426.5 P1Q15393-1
SF3B3ENST00000567654.1 linkuse as main transcriptc.161A>G p.Gln54Arg missense_variant 2/23

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 03, 2024The c.356A>G (p.Q119R) alteration is located in exon 3 (coding exon 2) of the SF3B3 gene. This alteration results from a A to G substitution at nucleotide position 356, causing the glutamine (Q) at amino acid position 119 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
Pathogenic
0.83
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.21
Cadd
Pathogenic
26
Dann
Uncertain
1.0
DEOGEN2
Benign
0.23
T;.
Eigen
Pathogenic
0.96
Eigen_PC
Pathogenic
0.89
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Benign
0.052
D
MetaRNN
Pathogenic
0.84
D;D
MetaSVM
Uncertain
-0.11
T
MutationAssessor
Pathogenic
3.6
H;.
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.82
D
PROVEAN
Uncertain
-3.7
D;.
REVEL
Pathogenic
0.65
Sift
Uncertain
0.0010
D;.
Sift4G
Pathogenic
0.0010
D;D
Polyphen
0.99
D;.
Vest4
0.94
MutPred
0.54
Gain of MoRF binding (P = 0.028);.;
MVP
0.86
MPC
2.3
ClinPred
1.0
D
GERP RS
5.6
Varity_R
0.92
gMVP
0.92

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: chr16-70563061; API