rs587776544
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_022464.5(SIL1):c.936delG(p.Leu313CysfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,606 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
SIL1
NM_022464.5 frameshift
NM_022464.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -3.02
Publications
0 publications found
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]
SIL1 Gene-Disease associations (from GenCC):
- Marinesco-Sjogren syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 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 5-138951263-GC-G is Pathogenic according to our data. Variant chr5-138951263-GC-G is described in ClinVar as Pathogenic. ClinVar VariationId is 2054736.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_022464.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SIL1 | NM_022464.5 | MANE Select | c.936delG | p.Leu313CysfsTer4 | frameshift | Exon 9 of 10 | NP_071909.1 | ||
| SIL1 | NM_001037633.2 | c.936delG | p.Leu313CysfsTer4 | frameshift | Exon 10 of 11 | NP_001032722.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SIL1 | ENST00000394817.7 | TSL:1 MANE Select | c.936delG | p.Leu313CysfsTer4 | frameshift | Exon 9 of 10 | ENSP00000378294.2 | ||
| SIL1 | ENST00000509534.5 | TSL:5 | c.957delG | p.Leu320CysfsTer4 | frameshift | Exon 10 of 11 | ENSP00000426858.1 | ||
| SIL1 | ENST00000265195.9 | TSL:5 | c.936delG | p.Leu313CysfsTer4 | frameshift | Exon 10 of 11 | ENSP00000265195.5 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000501 AC: 1AN: 199616 AF XY: 0.00000929 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
199616
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 6.97e-7 AC: 1AN: 1434606Hom.: 0 Cov.: 32 AF XY: 0.00000141 AC XY: 1AN XY: 711194 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1434606
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
711194
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32888
American (AMR)
AF:
AC:
0
AN:
41010
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25566
East Asian (EAS)
AF:
AC:
0
AN:
38402
South Asian (SAS)
AF:
AC:
0
AN:
82426
European-Finnish (FIN)
AF:
AC:
0
AN:
51200
Middle Eastern (MID)
AF:
AC:
0
AN:
5732
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1097996
Other (OTH)
AF:
AC:
1
AN:
59386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
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2
0.00
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0.60
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0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Marinesco-Sjögren syndrome (1)
Computational scores
Source:
Name
Calibrated prediction
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Prediction
PhyloP100
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
Publications
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