rs1555546980
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM4PP3
The NM_000080.4(CHRNE):βc.384_389delβ(p.Leu129_Val130del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ). Synonymous variant affecting the same amino acid position (i.e. V128V) has been classified as Likely benign.
Frequency
Consequence
NM_000080.4 inframe_deletion
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNE | NM_000080.4 | c.384_389del | p.Leu129_Val130del | inframe_deletion | 5/12 | ENST00000649488.2 | |
C17orf107 | NM_001145536.2 | c.*1513_*1518del | 3_prime_UTR_variant | 3/3 | ENST00000381365.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNE | ENST00000649488.2 | c.384_389del | p.Leu129_Val130del | inframe_deletion | 5/12 | NM_000080.4 | P1 | ||
C17orf107 | ENST00000381365.4 | c.*1513_*1518del | 3_prime_UTR_variant | 3/3 | 2 | NM_001145536.2 | A2 | ||
CHRNE | ENST00000649830.1 | c.-550_-545del | 5_prime_UTR_variant | 5/11 | |||||
CHRNE | ENST00000575637.1 | n.205_210del | non_coding_transcript_exon_variant | 4/6 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461758Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727172
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 4A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 03, 2022 | This variant, c.384_389del, results in the deletion of 2 amino acid(s) of the CHRNE protein (p.Leu129_Val130del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHRNE-related conditions. ClinVar contains an entry for this variant (Variation ID: 447041). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 23, 2022 | Available data are insufficient to determine the clinical significance of the variant at this time. This variant has not been reported in large, multi-ethnic general populations. Computational tools predict that this variant is damaging. The variant is located in a region that is considered important for protein function and/or structure. - |
Congenital myasthenic syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 08, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at