chr22-30338890-TG-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_005877.6(SF3A1):c.1641del(p.Ser548AlafsTer66) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
SF3A1
NM_005877.6 frameshift
NM_005877.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.435
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 Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 22-30338890-TG-T is Pathogenic according to our data. Variant chr22-30338890-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 2671887.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SF3A1 | NM_005877.6 | c.1641del | p.Ser548AlafsTer66 | frameshift_variant | 11/16 | ENST00000215793.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SF3A1 | ENST00000215793.13 | c.1641del | p.Ser548AlafsTer66 | frameshift_variant | 11/16 | 1 | NM_005877.6 | P1 | |
SF3A1 | ENST00000444440.1 | c.594del | p.Ser199AlafsTer? | frameshift_variant | 4/5 | 5 | |||
SF3A1 | ENST00000485618.1 | n.542del | non_coding_transcript_exon_variant | 3/3 | 2 | ||||
SF3A1 | ENST00000411423.1 | c.*140del | 3_prime_UTR_variant, NMD_transcript_variant | 3/4 | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Malignant lymphoma, large B-cell, diffuse Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Department Of Pathology & Laboratory Medicine, University Of Pennsylvania | Dec 04, 2023 | Post-initial therapy specimen. This represents a frameshift deletion occuring in this splicosome factor at exon 11 of 12, predicted to cause loss of function. Alterations in SF3A1 function are predicted to be disease associated in multiple cancers, likely mediated through interference of the splicing of oncogenes/tumor suppressor transcripts (PMID 26498691). SF3A1 frameshift deletions have been reported in Gallbladder and Stomach carcinomas (PMID 22037554 and 33563892). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.