rs371719657
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_003900.5(SQSTM1):c.332C>T(p.Pro111Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,613,108 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P111P) has been classified as Likely benign.
Frequency
Consequence
NM_003900.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SQSTM1 | NM_003900.5 | c.332C>T | p.Pro111Leu | missense_variant | 3/8 | ENST00000389805.9 | |
SQSTM1 | NM_001142298.2 | c.80C>T | p.Pro27Leu | missense_variant | 4/9 | ||
SQSTM1 | NM_001142299.2 | c.80C>T | p.Pro27Leu | missense_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SQSTM1 | ENST00000389805.9 | c.332C>T | p.Pro111Leu | missense_variant | 3/8 | 1 | NM_003900.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000722 AC: 11AN: 152256Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000320 AC: 8AN: 250104Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135416
GnomAD4 exome AF: 0.0000623 AC: 91AN: 1460852Hom.: 0 Cov.: 31 AF XY: 0.0000633 AC XY: 46AN XY: 726778
GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74392
ClinVar
Submissions by phenotype
Frontotemporal dementia and/or amyotrophic lateral sclerosis 1;C4085251:Paget disease of bone 2, early-onset Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 16, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 475401). This variant is also known as p.P27L. This missense change has been observed in individual(s) with dementia with Lewy bodies (PMID: 26836416, 31996268). This variant is present in population databases (rs371719657, gnomAD 0.009%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 111 of the SQSTM1 protein (p.Pro111Leu). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 03, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26836416, 31996268) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at