rs201820739

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_000055.4(BCHE):​c.428G>T​(p.Gly143Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

BCHE
NM_000055.4 missense

Scores

16
2
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.80
Variant links:
Genes affected
BCHE (HGNC:983): (butyrylcholinesterase) This gene encodes a cholinesterase enzyme and member of the type-B carboxylesterase/lipase family of proteins. The encoded enzyme exhibits broad substrate specificity and is involved in the detoxification of poisons including organophosphate nerve agents and pesticides, and the metabolism of drugs including cocaine, heroin and aspirin. Humans homozygous for certain mutations in this gene exhibit prolonged apnea after administration of the muscle relaxant succinylcholine. [provided by RefSeq, Jul 2016]
LINC01322 (HGNC:50528): (long intergenic non-protein coding RNA 1322)

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.993

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BCHENM_000055.4 linkc.428G>T p.Gly143Val missense_variant Exon 2 of 4 ENST00000264381.8 NP_000046.1 P06276
BCHENR_137636.2 linkn.546G>T non_coding_transcript_exon_variant Exon 2 of 5
BCHENR_137635.2 linkn.110+6708G>T intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BCHEENST00000264381.8 linkc.428G>T p.Gly143Val missense_variant Exon 2 of 4 1 NM_000055.4 ENSP00000264381.3 P06276

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461730
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727162
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Pathogenic
0.58
D
BayesDel_noAF
Pathogenic
0.59
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.91
D
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
0.99
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Pathogenic
0.43
D
MetaRNN
Pathogenic
0.99
D
MetaSVM
Pathogenic
0.92
D
MutationAssessor
Pathogenic
5.0
H
PrimateAI
Uncertain
0.64
T
PROVEAN
Pathogenic
-8.8
D
REVEL
Pathogenic
0.97
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.98
MutPred
0.96
Loss of disorder (P = 0.0649);
MVP
1.0
MPC
0.11
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.99
gMVP
0.92

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-165548394; API