rs1303974609

Variant names:

• chr16-66963315-C-A
• NM_024922.6:c.219C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-66963315-C-A
• chr16-66963315-C-G
• chr16-66963315-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024922.6(CES3):​c.219C>A​(p.Asp73Glu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CES3 NM_024922.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177

Genes affected

CES3 (HGNC:1865): (carboxylesterase 3) This gene encodes a member of the carboxylesterase large family. The family members are responsible for the hydrolysis or transesterification of various xenobiotics, such as cocaine and heroin, and endogenous substrates with ester, thioester, or amide bonds. They may participate in fatty acyl and cholesterol ester metabolism, and may play a role in the blood-brain barrier system. This gene is expressed in several tissues, particularly in colon, trachea and in brain, and the protein participates in colon and neural drug metabolism. Multiple alternatively spliced transcript variants encoding distinct isoforms have been reported, but the biological validity and/or full-length nature of some variants have not been determined.[provided by RefSeq, Jun 2010]

ENSG00000265408 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17399168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CES3	NM_024922.6	c.219C>A	p.Asp73Glu	missense_variant	Exon 2 of 13	ENST00000303334.9	NP_079198.2
CES3	NM_001185177.2	c.219C>A	p.Asp73Glu	missense_variant	Exon 2 of 13		NP_001172106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CES3	ENST00000303334.9	c.219C>A	p.Asp73Glu	missense_variant	Exon 2 of 13	1	NM_024922.6	ENSP00000304782.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.3
DANN	Benign	0.96
DEOGEN2	Benign	0.099	T;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.064	N
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.26	N;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.26	N;N
REVEL	Benign	0.13
Sift	Uncertain	0.011	D;D
Sift4G	Benign	0.24	T;T
Polyphen		0.0080	B;.
Vest4		0.11
MutPred		0.54		Gain of catalytic residue at D73 (P = 0.0865);Gain of catalytic residue at D73 (P = 0.0865);
MVP		0.39
MPC		0.17
ClinPred		0.29	T
GERP RS		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.060
gMVP		0.44

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: chr16-66997218;