5-138951263-G-GC
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Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_022464.5(SIL1):c.936_937insG(p.Leu313AlafsTer39) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,586,842 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
SIL1
NM_022464.5 frameshift
NM_022464.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -3.02
Genes affected
SIL1 (HGNC:24624): (SIL1 nucleotide exchange factor) This gene encodes a resident endoplasmic reticulum (ER), N-linked glycoprotein with an N-terminal ER targeting sequence, 2 putative N-glycosylation sites, and a C-terminal ER retention signal. This protein functions as a nucleotide exchange factor for another unfolded protein response protein. Mutations in this gene have been associated with Marinesco-Sjogren syndrome. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 8 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 5-138951263-G-GC is Pathogenic according to our data. Variant chr5-138951263-G-GC is described in ClinVar as [Pathogenic]. Clinvar id is 2629.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIL1 | NM_022464.5 | c.936_937insG | p.Leu313AlafsTer39 | frameshift_variant | 9/10 | ENST00000394817.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIL1 | ENST00000394817.7 | c.936_937insG | p.Leu313AlafsTer39 | frameshift_variant | 9/10 | 1 | NM_022464.5 | P1 | |
SIL1 | ENST00000265195.9 | c.936_937insG | p.Leu313AlafsTer39 | frameshift_variant | 10/11 | 5 | P1 | ||
SIL1 | ENST00000509534.5 | c.957_958insG | p.Leu320AlafsTer39 | frameshift_variant | 10/11 | 5 | |||
SIL1 | ENST00000515008.1 | n.271_272insG | non_coding_transcript_exon_variant | 3/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152238Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000501 AC: 1AN: 199616Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 107680
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GnomAD4 exome AF: 0.0000167 AC: 24AN: 1434604Hom.: 0 Cov.: 32 AF XY: 0.0000169 AC XY: 12AN XY: 711192
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74382
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Marinesco-Sjögren syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 15, 2014 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at