17-50136017-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_032595.5(PPP1R9B):c.2254G>A(p.Glu752Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 8/13 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_032595.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 35
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
PPP1R9B-related disorder Uncertain:1
The PPP1R9B c.2254G>A variant is predicted to result in the amino acid substitution p.Ala752Thr. This variant has been detected with de novo occurrence in four large autism sequencing cohorts (described using hg19 coordinates 17:48213378:C:T or hg38 coordinates 17:50136013:C:T), but based on the patient ID#s given in the studies there are actually only two separate individuals being reported (Yuen et al. 2016. PubMed ID: 27525107, S3- Table S4; Satterstrom et al. 2020. PubMed ID: 31981491, Table S1; Fu et al. 2022. PubMed ID: 35982160, Supplementary Table 20; Zhou et al. 2022. PubMed ID: 35982159, Supp Data 1). This variant was also detected de novo in an internal case, but the phenotype was not consistent with PPP1R9B- related disease (Internal Data, PreventionGenetics). This variant is documented in one allele in gnomAD (0.0032% of alleles in individuals of Latino descent). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at