chr3-165830222-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_000055.4(BCHE):c.812C>T(p.Thr271Met) variant causes a missense change. The variant allele was found at a frequency of 0.000747 in 1,613,898 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000055.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BCHE | NM_000055.4 | c.812C>T | p.Thr271Met | missense_variant | Exon 2 of 4 | ENST00000264381.8 | NP_000046.1 | |
BCHE | NR_137636.2 | n.930C>T | non_coding_transcript_exon_variant | Exon 2 of 5 | ||||
BCHE | NR_137635.2 | n.110+7092C>T | intron_variant | Intron 1 of 2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000585 AC: 89AN: 152102Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000439 AC: 110AN: 250754Hom.: 0 AF XY: 0.000450 AC XY: 61AN XY: 135504
GnomAD4 exome AF: 0.000764 AC: 1117AN: 1461678Hom.: 0 Cov.: 31 AF XY: 0.000743 AC XY: 540AN XY: 727132
GnomAD4 genome AF: 0.000585 AC: 89AN: 152220Hom.: 1 Cov.: 32 AF XY: 0.000726 AC XY: 54AN XY: 74408
ClinVar
Submissions by phenotype
Deficiency of butyrylcholinesterase Pathogenic:2
Variant summary: BCHE c.812C>T (p.Thr271Met, legacy name Thr243Met or the flu-1 allele) results in a non-conservative amino acid change located in the Carboxylesterase, type B domain (IPR002018) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00044 in 250754 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in BCHE causing Deficiency of butyrylcholine esterase (0.00044 vs 0.016), allowing no conclusion about variant significance. c.812C>T has been reported in the literature among compound heterozygous individuals affected with a deficiency of butyrylcholine esterase manifesting as the fluoride-resistant phenotype (example, Nogueira_1992, Yen_2003 and LaDu_1990). It has subsequently been cited in the literature (example, LaDu_1991 and Lando_2003). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported although a decrease in the number of carbohydrate chains per subunit, from nine to eight, has been attributed to the loss of Threonine residue in this variant (Nogueira_1992). The following publications have been ascertained in the context of this evaluation (PMID: 2013061, 2253336, 12724618, 1415224, 12881446, 33010031). ClinVar contains an entry for this variant (Variation ID: 13218). Based on the evidence outlined above, the variant was classified as likely pathogenic. -
The BCHE c.812C>T (p.Thr271Met) missense variant, also known as p.Thr243Met, is one of two known fluoride-resistant variants that affect sensitivity to succinylcholine. This variant has been reported in at least three studies and was found in a total of five probands, including in four in a compound heterozygous state, two of whom were related, and in one in a heterozygous state (Nogueira et al. 1992; Lando et al. 2003; Yen et al. 2003). Two additional related individuals with this variant were also reported by La Du et al. (1990). Control data are not available for this variant, which is reported at a frequency of 0.00091 in the African American population of the Exome Sequencing Project. The p.Thr271Met variant affects a glycosylation site on the BCHE protein, reducing the number of carbohydrate chains attached to the mature protein (Nogueira et al. 1992). Based on the evidence, the p.Thr271Met variant is classified as likely pathogenic for butyrylcholinesterase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. -
BCHE, flouride 1 Pathogenic:1
- -
not provided Uncertain:1
Classified by the PharmGKB project as a polymorphism associated with prolonged apnea, with alternate names listed as F-Variant, BCHE*243M, and Thr243Met (PMID: 26398623); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 2253336, 11928765, 13711731, 15563885, 12724618, 2013061, 12881446, 31589614, 37079615, 1415224, 26398623, 33010031) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at