chr5-179836493-A-AT
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_003900.5(SQSTM1):c.1224dup(p.Glu409Ter) 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 (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
SQSTM1
NM_003900.5 frameshift
NM_003900.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.341
Genes affected
SQSTM1 (HGNC:11280): (sequestosome 1) This gene encodes a multifunctional protein that binds ubiquitin and regulates activation of the nuclear factor kappa-B (NF-kB) signaling pathway. The protein functions as a scaffolding/adaptor protein in concert with TNF receptor-associated factor 6 to mediate activation of NF-kB in response to upstream signals. Alternatively spliced transcript variants encoding either the same or different isoforms have been identified for this gene. Mutations in this gene result in sporadic and familial Paget disease of bone. [provided by RefSeq, Mar 2009]
MRNIP (HGNC:30817): (MRN complex interacting protein) Enables chromatin binding activity. Involved in several processes, including mitotic G2 DNA damage checkpoint signaling; regulation of double-strand break repair; and response to ionizing radiation. Located in nucleoplasm. Colocalizes with Mre11 complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.538 CDS is truncated, and there are 3 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 5-179836493-A-AT is Pathogenic according to our data. Variant chr5-179836493-A-AT is described in ClinVar as [Pathogenic]. Clinvar id is 8109.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SQSTM1 | NM_003900.5 | c.1224dup | p.Glu409Ter | frameshift_variant | 8/8 | ENST00000389805.9 | |
SQSTM1 | NM_001142298.2 | c.972dup | p.Glu325Ter | frameshift_variant | 9/9 | ||
SQSTM1 | NM_001142299.2 | c.972dup | p.Glu325Ter | frameshift_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SQSTM1 | ENST00000389805.9 | c.1224dup | p.Glu409Ter | frameshift_variant | 8/8 | 1 | NM_003900.5 | P1 | |
SQSTM1 | ENST00000360718.5 | c.972dup | p.Glu325Ter | frameshift_variant | 7/7 | 1 | |||
MRNIP | ENST00000522663.5 | c.*1196_*1197insA | 3_prime_UTR_variant, NMD_transcript_variant | 9/9 | 1 | ||||
SQSTM1 | ENST00000510187.5 | c.974dup | p.Met325IlefsTer34 | frameshift_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Paget disease of bone 3 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 15, 2002 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at