1-204409645-CTTT-C
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_032833.5(PPP1R15B):βc.1764_1766delβ(p.Lys589del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,613,984 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ).
Frequency
Genomes: π 0.00014 ( 0 hom., cov: 32)
Exomes π: 0.00014 ( 0 hom. )
Consequence
PPP1R15B
NM_032833.5 inframe_deletion
NM_032833.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.373
Genes affected
PPP1R15B (HGNC:14951): (protein phosphatase 1 regulatory subunit 15B) This gene encodes a protein phosphatase I-interacting protein that promotes the dephosphorylation of eukaryotic translation initiation factor 2A to regulate translation under conditions of cellular stress. The transcribed messenger RNA contains two upstream open reading frames (ORFs) that repress translation of the main protein coding ORF under normal conditions, while the protein coding ORF is expressed at high levels in response to stress. Continual translation of the mRNA under conditions of eukaryotic translation initiation factor 2A inactivation is thought to create a feedback loop for reactivation of the gene during recovery from stress. In addition, it has been shown that this protein plays a role in membrane traffic that is independent of translation and that it is required for exocytosis from erythroleukemia cells. Allelic variants of this gene are associated with microcephaly, short stature, and impaired glucose metabolism. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_032833.5. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPP1R15B | NM_032833.5 | c.1764_1766del | p.Lys589del | inframe_deletion | 1/2 | ENST00000367188.5 | |
PPP1R15B | XM_005245551.6 | c.1764_1766del | p.Lys589del | inframe_deletion | 1/3 | ||
PPP1R15B | XM_047432518.1 | c.1764_1766del | p.Lys589del | inframe_deletion | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPP1R15B | ENST00000367188.5 | c.1764_1766del | p.Lys589del | inframe_deletion | 1/2 | 1 | NM_032833.5 | P1 | |
PPP1R15B-AS1 | ENST00000443515.1 | n.147-25691_147-25689del | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152100Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251470Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135912
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GnomAD4 exome AF: 0.000142 AC: 207AN: 1461884Hom.: 0 AF XY: 0.000135 AC XY: 98AN XY: 727240
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GnomAD4 genome AF: 0.000138 AC: 21AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74302
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 07, 2022 | This variant has not been reported in the literature in individuals affected with PPP1R15B-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant is present in population databases (rs764878882, gnomAD 0.01%). This variant, c.1764_1766del, results in the deletion of 1 amino acid(s) of the PPP1R15B protein (p.Lys589del), but otherwise preserves the integrity of the reading frame. - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at