5-179820938-T-A
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_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 Uncertain_significance. Variant got 5 ACMG points.
PVS1
Start lost variant, next in-frame start position is after 1 pathogenic variants. Next in-frame start position is after 252 CDS bases. Genomic position: 179823004. Lost 0.190 part of the original CDS.
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SQSTM1 | NM_003900.5 | c.2T>A | p.Met1? | start_lost | Exon 1 of 8 | ENST00000389805.9 | NP_003891.1 | |
SQSTM1 | NM_001142298.2 | c.-47-2020T>A | intron_variant | Intron 2 of 8 | NP_001135770.1 | |||
SQSTM1 | NM_001142299.2 | c.-47-2020T>A | intron_variant | Intron 2 of 8 | NP_001135771.1 |
Ensembl
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
Oct 10, 2016
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
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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
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