22-30342845-A-G
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP2PP3_ModerateBS2
The NM_005877.6(SF3A1):āc.686T>Cā(p.Leu229Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,612,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.000019 ( 0 hom. )
Consequence
SF3A1
NM_005877.6 missense
NM_005877.6 missense
Scores
13
4
2
Clinical Significance
Conservation
PhyloP100: 7.11
Genes affected
SF3A1 (HGNC:10765): (splicing factor 3a subunit 1) This gene encodes a subunit of the splicing factor 3a protein complex. The splicing factor 3a heterotrimer is a component of the mature U2 small nuclear ribonucleoprotein particle (snRNP). U2 small nuclear ribonucleoproteins play a critical role in spliceosome assembly and pre-mRNA splicing. [provided by RefSeq, Aug 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PP2
Missense variant where missense usually causes diseases, SF3A1
PP3
MetaRNN computational evidence supports a deleterious effect, 0.877
BS2
High AC in GnomAdExome4 at 28 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SF3A1 | NM_005877.6 | c.686T>C | p.Leu229Pro | missense_variant | 5/16 | ENST00000215793.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SF3A1 | ENST00000215793.13 | c.686T>C | p.Leu229Pro | missense_variant | 5/16 | 1 | NM_005877.6 | P1 | |
SF3A1 | ENST00000471037.1 | n.257T>C | non_coding_transcript_exon_variant | 2/2 | 3 | ||||
SF3A1 | ENST00000411423.1 | c.64-3666T>C | intron_variant, NMD_transcript_variant | 4 | |||||
SF3A1 | ENST00000447376.1 | c.*28T>C | 3_prime_UTR_variant, NMD_transcript_variant | 3/4 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152072Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250940Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135718
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GnomAD4 exome AF: 0.0000192 AC: 28AN: 1460816Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 18AN XY: 726844
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152072Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74284
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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 | Dec 14, 2023 | The c.686T>C (p.L229P) alteration is located in exon 5 (coding exon 5) of the SF3A1 gene. This alteration results from a T to C substitution at nucleotide position 686, causing the leucine (L) at amino acid position 229 to be replaced by a proline (P). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of stability (P = 0.0071);
MVP
MPC
ClinPred
D
GERP RS
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