8-143918210-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_201384.3(PLEC):c.11611G>A(p.Gly3871Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,577,568 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G3871G) has been classified as Likely benign.
Frequency
Consequence
NM_201384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.11611G>A | p.Gly3871Ser | missense_variant | 32/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.11569G>A | p.Gly3857Ser | missense_variant | 32/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.11611G>A | p.Gly3871Ser | missense_variant | 32/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.11569G>A | p.Gly3857Ser | missense_variant | 32/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes AF: 0.000986 AC: 150AN: 152134Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00147 AC: 300AN: 204752Hom.: 0 AF XY: 0.00144 AC XY: 166AN XY: 114986
GnomAD4 exome AF: 0.00131 AC: 1872AN: 1425316Hom.: 2 Cov.: 56 AF XY: 0.00132 AC XY: 935AN XY: 707610
GnomAD4 genome AF: 0.000985 AC: 150AN: 152252Hom.: 0 Cov.: 33 AF XY: 0.000900 AC XY: 67AN XY: 74430
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | PLEC: BP4 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 06, 2021 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 23, 2021 | The c.11692G>A (p.G3898S) alteration is located in exon 33 (coding exon 32) of the PLEC gene. This alteration results from a G to A substitution at nucleotide position 11692, causing the glycine (G) at amino acid position 3898 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 10, 2015 | - - |
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 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at