rs119456967
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_022464.5(SIL1):c.1370T>C(p.Leu457Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,058 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
SIL1
NM_022464.5 missense
NM_022464.5 missense
Scores
2
10
6
Clinical Significance
Conservation
PhyloP100: 3.65
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 5-138947133-A-G is Pathogenic according to our data. Variant chr5-138947133-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 2628.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.1370T>C | p.Leu457Pro | missense_variant | 10/10 | ENST00000394817.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIL1 | ENST00000394817.7 | c.1370T>C | p.Leu457Pro | missense_variant | 10/10 | 1 | NM_022464.5 | P1 | |
SIL1 | ENST00000509534.5 | c.1391T>C | p.Leu464Pro | missense_variant | 11/11 | 5 | |||
SIL1 | ENST00000265195.9 | c.1370T>C | p.Leu457Pro | missense_variant | 11/11 | 5 | P1 | ||
SIL1 | ENST00000515008.1 | n.705T>C | non_coding_transcript_exon_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249886Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135228
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461058Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726812
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
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 | Aug 01, 2008 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
A;A;A
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;T
Polyphen
P;P;P
Vest4
MutPred
0.62
.;.;Loss of stability (P = 0.0178);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
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