5-179836448-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting
The NM_003900.5(SQSTM1):c.1178G>A(p.Arg393Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000254 in 1,614,154 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_003900.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SQSTM1 | NM_003900.5 | c.1178G>A | p.Arg393Gln | missense_variant | Exon 8 of 8 | ENST00000389805.9 | NP_003891.1 | |
SQSTM1 | NM_001142298.2 | c.926G>A | p.Arg309Gln | missense_variant | Exon 9 of 9 | NP_001135770.1 | ||
SQSTM1 | NM_001142299.2 | c.926G>A | p.Arg309Gln | missense_variant | Exon 9 of 9 | NP_001135771.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152150Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000558 AC: 14AN: 251086Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135742
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 727246
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152268Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74452
ClinVar
Submissions by phenotype
SQSTM1-related disorder Uncertain:1
The SQSTM1 c.1178G>A variant is predicted to result in the amino acid substitution p.Arg393Gln. This variant was reported in an individual with amyotrophic lateral sclerosis (Tripolszki et al 2019. PubMed ID: 31475037). This variant is reported in 0.023% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-179263448-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Paget disease of bone 2, early-onset;C5779877:Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 Uncertain:1
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 393 of the SQSTM1 protein (p.Arg393Gln). This variant is present in population databases (rs200551825, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SQSTM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 475395). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SQSTM1 protein function with a negative predictive value of 80%. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at