rs121909513
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_000080.4(CHRNE):โc.250C>Tโ(p.Arg84Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (โ โ ). Synonymous variant affecting the same amino acid position (i.e. R84R) has been classified as Uncertain significance. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000080.4 stop_gained
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.250C>T | p.Arg84Ter | stop_gained | 4/12 | ENST00000649488.2 | |
C17orf107 | NM_001145536.2 | c.*1778G>A | 3_prime_UTR_variant | 3/3 | ENST00000381365.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNE | ENST00000649488.2 | c.250C>T | p.Arg84Ter | stop_gained | 4/12 | NM_000080.4 | P1 | ||
C17orf107 | ENST00000381365.4 | c.*1778G>A | 3_prime_UTR_variant | 3/3 | 2 | NM_001145536.2 | A2 | ||
CHRNE | ENST00000649830.1 | c.-684C>T | 5_prime_UTR_variant | 4/11 | |||||
CHRNE | ENST00000575637.1 | n.71C>T | non_coding_transcript_exon_variant | 3/6 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152162Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251470Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135918
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461878Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3AN XY: 727246
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74310
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 4A Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 18, 2023 | This sequence change creates a premature translational stop signal (p.Arg84*) 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 (rs121909513, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with autosomal recessive congenital myasthenic syndrome (PMID: 9158150). It has also been observed to segregate with disease in related individuals. This variant is also known as ลยตR64X. ClinVar contains an entry for this variant (Variation ID: 18347). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Congenital myasthenic syndrome 4C Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 1997 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 15, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at