chr22-50581796-G-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_005198.5(CHKB):c.400C>T(p.Gln134Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,704 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 (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_005198.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHKB | NM_005198.5 | c.400C>T | p.Gln134Ter | stop_gained | 3/11 | ENST00000406938.3 | |
CHKB-CPT1B | NR_027928.2 | n.618C>T | non_coding_transcript_exon_variant | 3/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHKB | ENST00000406938.3 | c.400C>T | p.Gln134Ter | stop_gained | 3/11 | 1 | NM_005198.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249938Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135382
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461704Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727130
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Megaconial type congenital muscular dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 04, 2022 | This sequence change creates a premature translational stop signal (p.Gln134*) in the CHKB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHKB are known to be pathogenic (PMID: 21665002). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CHKB-related conditions. ClinVar contains an entry for this variant (Variation ID: 468473). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at