10-94283801-GA-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_016341.4(PLCE1):c.4809delA(p.Asp1604ThrfsTer24) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,234 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_016341.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000804 AC: 2AN: 248808Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134970
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459234Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 725984
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
This sequence change creates a premature translational stop signal (p.Asp1604Thrfs*24) in the PLCE1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PLCE1 are known to be pathogenic (PMID: 17086182, 20591883). This variant is present in population databases (rs777787687, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PLCE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2117035). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at