Genetic Variant BCHE:p.Ser594Thr (chr3-165773410-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000055.4(BCHE):c.1781G>C(p.Ser594Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S594I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BCHE
NM_000055.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.45

Publications

0 publications found

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]

BCHE links:

LINC01322 (HGNC:50528): (long intergenic non-protein coding RNA 1322)

LINC01322 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3853019).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000055.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCHE	NM_000055.4	MANE Select	c.1781G>C	p.Ser594Thr	missense	Exon 4 of 4	NP_000046.1	P06276
BCHE	NR_137635.2		n.374G>C		non_coding_transcript_exon	Exon 3 of 3
BCHE	NR_137636.2		n.1978G>C		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCHE	ENST00000264381.8	TSL:1 MANE Select	c.1781G>C	p.Ser594Thr	missense	Exon 4 of 4	ENSP00000264381.3	P06276
BCHE	ENST00000479451.5	TSL:1	c.371G>C	p.Ser124Thr	missense	Exon 3 of 3	ENSP00000418325.1	H0Y885
BCHE	ENST00000855337.1		c.1844G>C	p.Ser615Thr	missense	Exon 5 of 5	ENSP00000525396.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458588

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725654

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33404

American (AMR)

AF:

0.00

AC:

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39476

South Asian (SAS)

AF:

0.00

AC:

AN:

86066

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1109640

Other (OTH)

AF:

0.00

AC:

AN:

60236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.30

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.75

M_CAP

Benign

0.067

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.5

PhyloP100

3.4

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-0.40

REVEL

Benign

0.24

Sift

Uncertain

0.011

Sift4G

Uncertain

0.053

Polyphen

0.029

Vest4

0.15

MutPred

0.52

Gain of glycosylation at Y592 (P = 0.0507)

MVP

0.76

MPC

0.014

ClinPred

0.91

GERP RS

4.3

Varity_R

0.17

gMVP

0.33

Mutation Taster

=78/22

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over