rs397515386
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_006941.4(SOX10):c.743_744del(p.Glu248AlafsTer32) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
SOX10
NM_006941.4 frameshift
NM_006941.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.26
Genes affected
SOX10 (HGNC:11190): (SRY-box transcription factor 10) This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional activator after forming a protein complex with other proteins. This protein acts as a nucleocytoplasmic shuttle protein and is important for neural crest and peripheral nervous system development. Mutations in this gene are associated with Waardenburg-Shah and Waardenburg-Hirschsprung disease. [provided by RefSeq, Jul 2008]
POLR2F (HGNC:9193): (RNA polymerase II, I and III subunit F) This gene encodes the sixth largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. In yeast, this polymerase subunit, in combination with at least two other subunits, forms a structure that stabilizes the transcribing polymerase on the DNA template. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 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 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 49 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 22-37974151-GCT-G is Pathogenic according to our data. Variant chr22-37974151-GCT-G is described in ClinVar as [Pathogenic]. Clinvar id is 30254.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-37974151-GCT-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOX10 | NM_006941.4 | c.743_744del | p.Glu248AlafsTer32 | frameshift_variant | 4/4 | ENST00000396884.8 | |
POLR2F | NM_001301130.2 | c.293+6984_293+6985del | intron_variant | ||||
POLR2F | NM_001301131.2 | c.293+6984_293+6985del | intron_variant | ||||
POLR2F | NM_001363825.1 | c.*38+1844_*38+1845del | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOX10 | ENST00000396884.8 | c.743_744del | p.Glu248AlafsTer32 | frameshift_variant | 4/4 | 1 | NM_006941.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
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
Waardenburg syndrome type 2E, without neurologic involvement Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2012 | - - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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Calibrated prediction
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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