chr1-204406262-G-A
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2PM5PP3_StrongPP5_Moderate
The NM_032833.5(PPP1R15B):c.1972C>T(p.Arg658Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R658H) has been classified as Likely pathogenic.
Frequency
Consequence
NM_032833.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPP1R15B | NM_032833.5 | c.1972C>T | p.Arg658Cys | missense_variant | 2/2 | ENST00000367188.5 | |
PPP1R15B | XM_005245551.6 | c.1920+3230C>T | intron_variant | ||||
PPP1R15B | XM_047432518.1 | c.1920+3230C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPP1R15B | ENST00000367188.5 | c.1972C>T | p.Arg658Cys | missense_variant | 2/2 | 1 | NM_032833.5 | P1 | |
PPP1R15B-AS1 | ENST00000443515.1 | n.146+28267G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461804Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727202
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Microcephaly, short stature, and impaired glucose metabolism 2 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | 3billion | May 22, 2022 | The variant is not observed in the gnomAD v2.1.1 dataset. Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID: 26307080). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.68; 3Cnet: 0.94). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with PPP1R15B- related disorder (ClinVar ID: VCV000222030 / PMID: 26307080). A different missense change at the same codon (p.Arg658His) has been reported to be associated with PPP1R15B- related disorder (ClinVar ID: VCV000807902). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 16, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at