rs577419493
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_201384.3(PLEC):c.5213G>A(p.Arg1738Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000867 in 1,534,138 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. R1738W) has been classified as Uncertain significance.
Frequency
Consequence
NM_201384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.5213G>A | p.Arg1738Gln | missense_variant | 31/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.5171G>A | p.Arg1724Gln | missense_variant | 31/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.5213G>A | p.Arg1738Gln | missense_variant | 31/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.5171G>A | p.Arg1724Gln | missense_variant | 31/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes AF: 0.000461 AC: 70AN: 151968Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000778 AC: 10AN: 128614Hom.: 0 AF XY: 0.0000994 AC XY: 7AN XY: 70396
GnomAD4 exome AF: 0.0000456 AC: 63AN: 1382060Hom.: 0 Cov.: 68 AF XY: 0.0000411 AC XY: 28AN XY: 681932
GnomAD4 genome AF: 0.000460 AC: 70AN: 152078Hom.: 0 Cov.: 34 AF XY: 0.000403 AC XY: 30AN XY: 74350
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 15, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 31, 2023 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 15, 2023 | The c.5294G>A (p.R1765Q) alteration is located in exon 32 (coding exon 31) of the PLEC gene. This alteration results from a G to A substitution at nucleotide position 5294, causing the arginine (R) at amino acid position 1765 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
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 | Mar 16, 2023 | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 283286). This variant has not been reported in the literature in individuals affected with PLEC-related conditions. This variant is present in population databases (rs577419493, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1765 of the PLEC protein (p.Arg1765Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at