chr14-90263394-A-G
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_002802.3(PSMC1):c.231A>G(p.Glu77=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00329 in 1,593,456 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0030 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0033 ( 21 hom. )
Consequence
PSMC1
NM_002802.3 synonymous
NM_002802.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.300
Genes affected
PSMC1 (HGNC:9547): (proteasome 26S subunit, ATPase 1) The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes one of the ATPase subunits, a member of the triple-A family of ATPases which have a chaperone-like activity. This subunit and a 20S core alpha subunit interact specifically with the hepatitis B virus X protein, a protein critical to viral replication. This subunit also interacts with the adenovirus E1A protein and this interaction alters the activity of the proteasome. Finally, this subunit interacts with ataxin-7, suggesting a role for the proteasome in the development of spinocerebellar ataxia type 7, a progressive neurodegenerative disorder. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
Variant 14-90263394-A-G is Benign according to our data. Variant chr14-90263394-A-G is described in ClinVar as [Benign]. Clinvar id is 770241.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.3 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSMC1 | NM_002802.3 | c.231A>G | p.Glu77= | synonymous_variant | 4/11 | ENST00000261303.13 | |
PSMC1 | NM_001330212.2 | c.12A>G | p.Glu4= | synonymous_variant | 5/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSMC1 | ENST00000261303.13 | c.231A>G | p.Glu77= | synonymous_variant | 4/11 | 1 | NM_002802.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00300 AC: 456AN: 152246Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00346 AC: 813AN: 235156Hom.: 5 AF XY: 0.00341 AC XY: 435AN XY: 127458
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GnomAD4 exome AF: 0.00332 AC: 4781AN: 1441092Hom.: 21 Cov.: 31 AF XY: 0.00333 AC XY: 2385AN XY: 716742
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GnomAD4 genome ? AF: 0.00299 AC: 456AN: 152364Hom.: 1 Cov.: 33 AF XY: 0.00322 AC XY: 240AN XY: 74506
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at