rs765721225
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The ENST00000394817.7(SIL1):c.991C>T(p.Arg331Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000199 in 1,609,598 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R331R) has been classified as Likely benign.
Frequency
Consequence
ENST00000394817.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SIL1 | NM_022464.5 | c.991C>T | p.Arg331Cys | missense_variant | 9/10 | ENST00000394817.7 | NP_071909.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SIL1 | ENST00000394817.7 | c.991C>T | p.Arg331Cys | missense_variant | 9/10 | 1 | NM_022464.5 | ENSP00000378294 | P1 | |
SIL1 | ENST00000509534.5 | c.1012C>T | p.Arg338Cys | missense_variant | 10/11 | 5 | ENSP00000426858 | |||
SIL1 | ENST00000265195.9 | c.991C>T | p.Arg331Cys | missense_variant | 10/11 | 5 | ENSP00000265195 | P1 | ||
SIL1 | ENST00000515008.1 | n.326C>T | non_coding_transcript_exon_variant | 3/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152242Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000500 AC: 12AN: 240020Hom.: 0 AF XY: 0.0000538 AC XY: 7AN XY: 130024
GnomAD4 exome AF: 0.0000206 AC: 30AN: 1457356Hom.: 0 Cov.: 32 AF XY: 0.0000207 AC XY: 15AN XY: 724452
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74368
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 20, 2017 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 17, 2023 | The c.991C>T (p.R331C) alteration is located in exon 9 (coding exon 8) of the SIL1 gene. This alteration results from a C to T substitution at nucleotide position 991, causing the arginine (R) at amino acid position 331 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at