19-2247804-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_007165.5(SF3A2):c.653C>T(p.Pro218Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000777 in 1,609,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000078 ( 0 hom. )
Consequence
SF3A2
NM_007165.5 missense
NM_007165.5 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 5.02
Genes affected
SF3A2 (HGNC:10766): (splicing factor 3a subunit 2) This gene encodes subunit 2 of the splicing factor 3a protein complex. The splicing factor 3a heterotrimer includes subunits 1, 2 and 3 and is necessary for the in vitro conversion of 15S U2 snRNP into an active 17S particle that performs pre-mRNA splicing. Subunit 2 interacts with subunit 1 through its amino-terminus while the single zinc finger domain of subunit 2 plays a role in its binding to the 15S U2 snRNP. Subunit 2 may also function independently of its RNA splicing function as a microtubule-binding protein. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.009569347).
BS2
?
High AC in GnomAd4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SF3A2 | NM_007165.5 | c.653C>T | p.Pro218Leu | missense_variant | 9/9 | ENST00000221494.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SF3A2 | ENST00000221494.10 | c.653C>T | p.Pro218Leu | missense_variant | 9/9 | 1 | NM_007165.5 | P1 | |
SF3A2 | ENST00000592314.5 | n.811C>T | non_coding_transcript_exon_variant | 8/8 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000724 AC: 11AN: 152030Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000391 AC: 95AN: 242910Hom.: 0 AF XY: 0.000308 AC XY: 41AN XY: 133112
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GnomAD4 exome AF: 0.0000782 AC: 114AN: 1457642Hom.: 0 Cov.: 33 AF XY: 0.0000717 AC XY: 52AN XY: 725336
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GnomAD4 genome ? AF: 0.0000724 AC: 11AN: 152030Hom.: 0 Cov.: 33 AF XY: 0.0000539 AC XY: 4AN XY: 74246
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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 submitter | clinical testing | Ambry Genetics | Oct 22, 2021 | The c.653C>T (p.P218L) alteration is located in exon 9 (coding exon 8) of the SF3A2 gene. This alteration results from a C to T substitution at nucleotide position 653, causing the proline (P) at amino acid position 218 to be replaced by a leucine (L). 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
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Uncertain
T
Polyphen
B
Vest4
MutPred
Loss of catalytic residue at P217 (P = 0.0116);
MVP
MPC
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