17-4899229-C-CTCAAACA
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_000080.4(CHRNE):c.1187_1188insTGTTTGA(p.Glu396AspfsTer3) variant causes a stop gained, frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,454,918 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. E396E) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000080.4 stop_gained, frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNE | NM_000080.4 | c.1187_1188insTGTTTGA | p.Glu396AspfsTer3 | stop_gained, frameshift_variant | 10/12 | ENST00000649488.2 | |
CHRNE | XM_017024115.2 | c.1151_1152insTGTTTGA | p.Glu384AspfsTer3 | stop_gained, frameshift_variant | 11/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNE | ENST00000649488.2 | c.1187_1188insTGTTTGA | p.Glu396AspfsTer3 | stop_gained, frameshift_variant | 10/12 | NM_000080.4 | P1 | ||
CHRNE | ENST00000649830.1 | c.254_255insTGTTTGA | p.Glu85AspfsTer3 | stop_gained, frameshift_variant | 10/11 | ||||
CHRNE | ENST00000572438.1 | n.873_874insTGTTTGA | non_coding_transcript_exon_variant | 5/7 | 5 | ||||
CHRNE | ENST00000652550.1 | n.917_918insTGTTTGA | non_coding_transcript_exon_variant | 2/4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000421 AC: 1AN: 237386Hom.: 0 AF XY: 0.00000768 AC XY: 1AN XY: 130168
GnomAD4 exome AF: 0.00000412 AC: 6AN: 1454918Hom.: 0 Cov.: 35 AF XY: 0.00000414 AC XY: 3AN XY: 723882
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 4A Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 24, 2024 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 05, 2023 | This sequence change creates a premature translational stop signal (p.Glu396Aspfs*3) in the CHRNE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHRNE are known to be pathogenic (PMID: 22678886). This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with autosomal recessive congenital myasthenic syndrome (PMID: 28024842). ClinVar contains an entry for this variant (Variation ID: 465857). For these reasons, this variant has been classified as Pathogenic. - |
Congenital myasthenic syndrome 4C Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München | Jan 29, 2021 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jan 11, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at