rs140891877
Positions:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_ModerateBP6BP7BS1
The NM_022464.5(SIL1):c.699T>C(p.Asn233=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,614,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00020 ( 0 hom. )
Consequence
SIL1
NM_022464.5 synonymous
NM_022464.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0590
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_benign. Variant got -6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
Variant 5-139021239-A-G is Benign according to our data. Variant chr5-139021239-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 351082.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=0.059 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000199 (291/1461874) while in subpopulation SAS AF= 0.00147 (127/86258). AF 95% confidence interval is 0.00126. There are 0 homozygotes in gnomad4_exome. There are 181 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIL1 | NM_022464.5 | c.699T>C | p.Asn233= | synonymous_variant | 7/10 | ENST00000394817.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIL1 | ENST00000394817.7 | c.699T>C | p.Asn233= | synonymous_variant | 7/10 | 1 | NM_022464.5 | P1 | |
ENST00000512875.2 | n.445+4010A>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000237 AC: 36AN: 152180Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000342 AC: 86AN: 251338Hom.: 0 AF XY: 0.000405 AC XY: 55AN XY: 135840
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GnomAD4 exome AF: 0.000199 AC: 291AN: 1461874Hom.: 0 Cov.: 32 AF XY: 0.000249 AC XY: 181AN XY: 727240
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GnomAD4 genome ? AF: 0.000236 AC: 36AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.000295 AC XY: 22AN XY: 74480
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Marinesco-Sjögren syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 06, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 30, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 28, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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