rs374419983
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_201384.3(PLEC):c.46C>T(p.Arg16*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_201384.3 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 exomes AF: 0.00000814 AC: 2AN: 245668Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 134038
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1460370Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4AN XY: 726492
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Epidermolysis bullosa simplex with nail dystrophy Pathogenic:1
- -
Epidermolysis bullosa simplex 5C, with pyloric atresia Pathogenic:1
The stop gained PLEC c.46C>T variant has been reported in individuals affected with Epidermolysis bullosa simplex with pyloric atresia (Zrelski et al, 2021; Gostyńska et. al., 2015). Functional studies related to this variant have showed the expression of plectin isoforms (Gostyńska et. al., 2015; Castañón et. al., 2021). The c.46C>T variant is novel (not in any individuals) in 1000 Genomes and has allele frequency of 0.0008% in gnomAD database. This variant has been reported to the ClinVar database as Pathogenic. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic -
not provided Pathogenic:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at