NM_000055.4:c.1757A>G

Variant names:

• chr3-165773434-T-C
• NM_000055.4:c.1757A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000055.4(BCHE):​c.1757A>G​(p.Lys586Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BCHE NM_000055.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.72

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)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.271887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCHE	NM_000055.4	c.1757A>G	p.Lys586Arg	missense_variant	Exon 4 of 4	ENST00000264381.8	NP_000046.1
BCHE	NR_137635.2	n.350A>G		non_coding_transcript_exon_variant	Exon 3 of 3
BCHE	NR_137636.2	n.1954A>G		non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCHE	ENST00000264381.8	c.1757A>G	p.Lys586Arg	missense_variant	Exon 4 of 4	1	NM_000055.4	ENSP00000264381.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Sep 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1757A>G (p.K586R) alteration is located in exon 4 (coding exon 3) of the BCHE gene. This alteration results from a A to G substitution at nucleotide position 1757, causing the lysine (K) at amino acid position 586 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T;T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.60	N;N
REVEL	Benign	0.14
Sift	Benign	0.086	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.0010	B;.
Vest4		0.13
MutPred		0.54		Loss of methylation at K586 (P = 0.0068);.;
MVP		0.79
MPC		0.016
ClinPred		0.32	T
GERP RS		2.8
Varity_R		0.18
gMVP		0.55

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: chr3-165491222;