3-165829750-G-C

Variant names:

• chr3-165829750-G-C
• rs762341786
• NM_000055.4:c.1284C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000055.4(BCHE):​c.1284C>G​(p.Cys428Trp) 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 1,461,698 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: 0.0000014 (0 hom.)
• Consequence: BCHE NM_000055.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.931

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCHE	NM_000055.4	MANE Select	c.1284C>G	p.Cys428Trp	missense	Exon 2 of 4	NP_000046.1	P06276
	BCHE	NR_137636.2		n.1402C>G		non_coding_transcript_exon	Exon 2 of 5
	BCHE	NR_137635.2		n.110+7564C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCHE	ENST00000264381.8	TSL:1 MANE Select	c.1284C>G	p.Cys428Trp	missense	Exon 2 of 4	ENSP00000264381.3	P06276
	BCHE	ENST00000479451.5	TSL:1	c.107+7564C>G		intron	N/A	ENSP00000418325.1	H0Y885
	BCHE	ENST00000855337.1		c.1284C>G	p.Cys428Trp	missense	Exon 2 of 5	ENSP00000525396.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250692 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461698 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727130

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111894

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.78	D
Eigen	Benign	0.14
Eigen_PC	Benign	-0.040
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		-0.23
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-9.8	D
REVEL	Uncertain	0.53
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.79		Gain of glycosylation at Y424 (P = 0.1572)
MVP		0.97
MPC		0.11
ClinPred		1.0	D
GERP RS		0.62
Varity_R		0.99
gMVP		0.96
Mutation Taster		=23/77	disease causing

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

Other links and lift over

dbSNP: rs762341786; hg19: chr3-165547538;