rs886039780
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PS1_ModeratePM2PP5
The NM_003900.5(SQSTM1):c.2T>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 34)
Consequence
SQSTM1
NM_003900.5 start_lost
NM_003900.5 start_lost
Scores
6
4
6
Clinical Significance
Conservation
PhyloP100: 2.30
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 13 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PS1
?
Another start lost variant in NM_003900.5 (SQSTM1) was described as [Conflicting_classifications_of_pathogenicity] in ClinVar as 1019776
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 5-179820938-T-A is Pathogenic according to our data. Variant chr5-179820938-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 265780.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.2T>A | p.Met1? | start_lost | 1/8 | ENST00000389805.9 | |
SQSTM1 | NM_001142298.2 | c.-47-2020T>A | intron_variant | ||||
SQSTM1 | NM_001142299.2 | c.-47-2020T>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SQSTM1 | ENST00000389805.9 | c.2T>A | p.Met1? | start_lost | 1/8 | 1 | NM_003900.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 10, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D;.
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PROVEAN
Benign
N;.;N;N
REVEL
Benign
Sift
Pathogenic
D;.;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
B;.;.;P
Vest4
MutPred
Gain of MoRF binding (P = 0.0249);Gain of MoRF binding (P = 0.0249);Gain of MoRF binding (P = 0.0249);Gain of MoRF binding (P = 0.0249);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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