5-179836442-AC-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_003900.5(SQSTM1):c.1175delC(p.Pro392ArgfsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. P392P) has been classified as Likely benign.
Frequency
Consequence
NM_003900.5 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SQSTM1 | NM_003900.5 | c.1175delC | p.Pro392ArgfsTer3 | frameshift_variant | Exon 8 of 8 | ENST00000389805.9 | NP_003891.1 | |
SQSTM1 | NM_001142298.2 | c.923delC | p.Pro308ArgfsTer3 | frameshift_variant | Exon 9 of 9 | NP_001135770.1 | ||
SQSTM1 | NM_001142299.2 | c.923delC | p.Pro308ArgfsTer3 | frameshift_variant | Exon 9 of 9 | NP_001135771.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Paget disease of bone 2, early-onset;C5779877:Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the region of the SQSTM1 protein between codon 391 and 396. Other variants in this region have been observed in individuals with autosomal dominant SQSTM1-related conditions (PMID: 12374763, 14584883, 25664955), which suggests that this may be a clinically significant region of the protein. This variant is also known as 1215delC. This premature translational stop signal has been observed in individual(s) with Paget’s disease of bone (PMID: 14584883). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro392Argfs*3) in the SQSTM1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 49 amino acid(s) of the SQSTM1 protein. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.