rs143956614
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_003900.5(SQSTM1):āc.1108T>Cā(p.Ser370Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000365 in 1,614,078 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_003900.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SQSTM1 | NM_003900.5 | c.1108T>C | p.Ser370Pro | missense_variant | 7/8 | ENST00000389805.9 | NP_003891.1 | |
SQSTM1 | NM_001142298.2 | c.856T>C | p.Ser286Pro | missense_variant | 8/9 | NP_001135770.1 | ||
SQSTM1 | NM_001142299.2 | c.856T>C | p.Ser286Pro | missense_variant | 8/9 | NP_001135771.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SQSTM1 | ENST00000389805.9 | c.1108T>C | p.Ser370Pro | missense_variant | 7/8 | 1 | NM_003900.5 | ENSP00000374455.4 | ||
SQSTM1 | ENST00000360718.5 | c.856T>C | p.Ser286Pro | missense_variant | 6/7 | 1 | ENSP00000353944.5 | |||
SQSTM1 | ENST00000510187.5 | c.950+498T>C | intron_variant | 5 | ENSP00000424477.1 |
Frequencies
GnomAD3 genomes AF: 0.00203 AC: 308AN: 152082Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000489 AC: 123AN: 251412Hom.: 0 AF XY: 0.000331 AC XY: 45AN XY: 135894
GnomAD4 exome AF: 0.000192 AC: 281AN: 1461878Hom.: 3 Cov.: 33 AF XY: 0.000154 AC XY: 112AN XY: 727240
GnomAD4 genome AF: 0.00202 AC: 308AN: 152200Hom.: 2 Cov.: 32 AF XY: 0.00185 AC XY: 138AN XY: 74400
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Paget disease of bone 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 27, 2017 | - - |
SQSTM1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 23, 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
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at