rs121912820
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3_ModeratePP5
The NM_020549.5(CHAT):āc.629T>Cā(p.Leu210Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,613,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. L210L) has been classified as Likely benign.
Frequency
Consequence
NM_020549.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHAT | NM_020549.5 | c.629T>C | p.Leu210Pro | missense_variant | 4/15 | ENST00000337653.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHAT | ENST00000337653.7 | c.629T>C | p.Leu210Pro | missense_variant | 4/15 | 1 | NM_020549.5 | P2 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152144Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000123 AC: 31AN: 251452Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135902
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461670Hom.: 0 Cov.: 32 AF XY: 0.0000413 AC XY: 30AN XY: 727140
GnomAD4 genome AF: 0.000105 AC: 16AN: 152144Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74320
ClinVar
Submissions by phenotype
Familial infantile myasthenia Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 13, 2001 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at