rs375495050
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBS2_Supporting
The NM_003900.5(SQSTM1):c.1088G>A(p.Gly363Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000669 in 1,614,006 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G363R) has been classified as Uncertain significance.
Frequency
Consequence
NM_003900.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SQSTM1 | NM_003900.5 | c.1088G>A | p.Gly363Glu | missense_variant | 7/8 | ENST00000389805.9 | |
SQSTM1 | NM_001142298.2 | c.836G>A | p.Gly279Glu | missense_variant | 8/9 | ||
SQSTM1 | NM_001142299.2 | c.836G>A | p.Gly279Glu | missense_variant | 8/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SQSTM1 | ENST00000389805.9 | c.1088G>A | p.Gly363Glu | missense_variant | 7/8 | 1 | NM_003900.5 | P1 | |
SQSTM1 | ENST00000360718.5 | c.836G>A | p.Gly279Glu | missense_variant | 6/7 | 1 | |||
SQSTM1 | ENST00000510187.5 | c.950+478G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152120Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000342 AC: 86AN: 251430Hom.: 1 AF XY: 0.000280 AC XY: 38AN XY: 135902
GnomAD4 exome AF: 0.0000684 AC: 100AN: 1461886Hom.: 1 Cov.: 33 AF XY: 0.0000591 AC XY: 43AN XY: 727244
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74314
ClinVar
Submissions by phenotype
SQSTM1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 27, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Paget disease of bone 2, early-onset;C5779877:Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at