5-179836439-CT-C
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 12P and 1B. PVS1_StrongPP5_Very_StrongBS2_Supporting
The NM_003900.5(SQSTM1):c.1170delT(p.Asp391ThrfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_003900.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SQSTM1 | NM_003900.5 | c.1170delT | p.Asp391ThrfsTer4 | frameshift_variant | Exon 8 of 8 | ENST00000389805.9 | NP_003891.1 | |
SQSTM1 | NM_001142298.2 | c.918delT | p.Asp307ThrfsTer4 | frameshift_variant | Exon 9 of 9 | NP_001135770.1 | ||
SQSTM1 | NM_001142299.2 | c.918delT | p.Asp307ThrfsTer4 | frameshift_variant | Exon 9 of 9 | NP_001135771.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461880Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727240
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
This premature translational stop signal has been observed in individual(s) with autosomal dominant Paget's disease of bone (PMID: 14584883). It has also been observed to segregate with disease in related individuals. This variant is also known as 1210delT. ClinVar contains an entry for this variant (Variation ID: 1069495). For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp391Thrfs*4) in the SQSTM1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 50 amino acid(s) of the SQSTM1 protein. -
not provided Pathogenic:1
SQSTM1: PVS1:Strong, PM2 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at