3-165830879-G-T

Variant names:

• chr3-165830879-G-T
• rs56309853
• NM_000055.4:c.155C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000055.4(BCHE):​c.155C>A​(p.Thr52Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,670 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T52M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: BCHE NM_000055.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.36
• Publications: 3 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.155C>A	p.Thr52Lys	missense	Exon 2 of 4	NP_000046.1	P06276
	BCHE	NR_137636.2		n.273C>A		non_coding_transcript_exon	Exon 2 of 5
	BCHE	NR_137635.2		n.110+6435C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCHE	ENST00000264381.8	TSL:1 MANE Select	c.155C>A	p.Thr52Lys	missense	Exon 2 of 4	ENSP00000264381.3	P06276
	BCHE	ENST00000479451.5	TSL:1	c.107+6435C>A		intron	N/A	ENSP00000418325.1	H0Y885
	BCHE	ENST00000855337.1		c.155C>A	p.Thr52Lys	missense	Exon 2 of 5	ENSP00000525396.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251192 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461670 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727124

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.0000671 AC: 3 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

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: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111892

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.0018	T
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	14
DANN	Benign	0.24
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.086	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Uncertain	0.022	D
MutationAssessor	Benign	0.42	N
PhyloP100		3.4
PrimateAI	Benign	0.45	T
PROVEAN	Benign	1.2	N
REVEL	Uncertain	0.52
Sift	Benign	1.0	T
Sift4G	Benign	0.98	T
Polyphen		0.61	P
Vest4		0.52
MutPred		0.53		Gain of methylation at T52 (P = 0.0207)
MVP		1.0
MPC		0.017
ClinPred		0.075	T
GERP RS		4.9
Varity_R		0.42
gMVP		0.66
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.23		Position offset: -1

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

Other links and lift over

dbSNP: rs56309853; hg19: chr3-165548667;