5-139050960-G-A
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_022464.5(SIL1):c.331C>T(p.Arg111Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_022464.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIL1 | NM_022464.5 | c.331C>T | p.Arg111Ter | stop_gained | 4/10 | ENST00000394817.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIL1 | ENST00000394817.7 | c.331C>T | p.Arg111Ter | stop_gained | 4/10 | 1 | NM_022464.5 | P1 | |
ENST00000512875.2 | n.530-42G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152048Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251494Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135922
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461842Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727230
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74394
ClinVar
Submissions by phenotype
Marinesco-Sjögren syndrome Pathogenic:3
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2007 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 11, 2019 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2022 | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 2625). This premature translational stop signal has been observed in individual(s) with Marinesco-Sjogren syndrome (PMID: 16282977, 21873089). This variant is present in population databases (rs119456965, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Arg111*) in the SIL1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SIL1 are known to be pathogenic (PMID: 16282977, 24176978). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at