rs200788163
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_017934.7(PHIP):c.2902C>T(p.Arg968*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000187 in 1,602,582 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 Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_017934.7 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151906Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000828 AC: 2AN: 241534Hom.: 0 AF XY: 0.0000153 AC XY: 2AN XY: 130362
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1450560Hom.: 0 Cov.: 28 AF XY: 0.00000277 AC XY: 2AN XY: 721374
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152022Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74314
ClinVar
Submissions by phenotype
PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome Pathogenic:3
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not provided Pathogenic:1
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 31345219, 33867250, 29209020) -
PHIP-related disorder Pathogenic:1
The PHIP c.2902C>T variant is predicted to result in premature protein termination (p.Arg968*). This variant was reported in two unrelated individuals with developmental delay, obesity, and dysmorphism; and in at least one case, this variant was observed de novo (Jansen et al. 2018. PubMed ID: 29209020; Kaur et al. 2021. PubMed ID: 33867250). This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Nonsense variants in PHIP are expected to be pathogenic. This variant is interpreted as likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at