chr1-149923669-TG-T
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_005850.5(SF3B4):c.1147del(p.His383MetfsTer75) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SF3B4
NM_005850.5 frameshift
NM_005850.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.85
Genes affected
SF3B4 (HGNC:10771): (splicing factor 3b subunit 4) This gene encodes one of four subunits of the splicing factor 3B. The protein encoded by this gene cross-links to a region in the pre-mRNA immediately upstream of the branchpoint sequence in pre-mRNA in the prespliceosomal complex A. It also may be involved in the assembly of the B, C and E spliceosomal complexes. In addition to RNA-binding activity, this protein interacts directly and highly specifically with subunit 2 of the splicing factor 3B. This protein contains two N-terminal RNA-recognition motifs (RRMs), consistent with the observation that it binds directly to pre-mRNA. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 14 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-149923669-TG-T is Pathogenic according to our data. Variant chr1-149923669-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 31652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-149923669-TG-T is described in Lovd as [Likely_pathogenic]. Variant chr1-149923669-TG-T is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SF3B4 | NM_005850.5 | c.1147del | p.His383MetfsTer75 | frameshift_variant | 6/6 | ENST00000271628.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SF3B4 | ENST00000271628.9 | c.1147del | p.His383MetfsTer75 | frameshift_variant | 6/6 | 1 | NM_005850.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1374610Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 681490
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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0
AN:
1374610
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Cov.:
32
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0
AN XY:
681490
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Nager syndrome Pathogenic:2
Pathogenic, no assertion criteria provided | research | Clinical Genetics Research Group, University of Calgary | Sep 07, 2012 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2013 | - - |
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | May 01, 2017 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen | Oct 23, 2020 | - - |
Computational scores
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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