rs1554708450
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_201384.3(PLEC):c.3436T>A(p.Phe1146Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000277 in 1,444,052 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F1146L) has been classified as Uncertain significance.
Frequency
Consequence
NM_201384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.3436T>A | p.Phe1146Ile | missense_variant | 27/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.3394T>A | p.Phe1132Ile | missense_variant | 27/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.3436T>A | p.Phe1146Ile | missense_variant | 27/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.3394T>A | p.Phe1132Ile | missense_variant | 27/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 exomes AF: 0.00000919 AC: 2AN: 217746Hom.: 0 AF XY: 0.00000834 AC XY: 1AN XY: 119922
GnomAD4 exome AF: 0.00000277 AC: 4AN: 1444052Hom.: 0 Cov.: 34 AF XY: 0.00000279 AC XY: 2AN XY: 716206
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Epidermolysis bullosa simplex, Ogna type;C2677349:Epidermolysis bullosa simplex 5C, with pyloric atresia;C2931072:Epidermolysis bullosa simplex 5B, with muscular dystrophy;C3150989:Autosomal recessive limb-girdle muscular dystrophy type 2Q;C4225309:Epidermolysis bullosa simplex with nail dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PLEC protein function. ClinVar contains an entry for this variant (Variation ID: 538930). This variant has not been reported in the literature in individuals affected with PLEC-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces phenylalanine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1173 of the PLEC protein (p.Phe1173Ile). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 18, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at