chr16-55828771-G-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001025195.2(CES1):c.256C>A(p.Pro86Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 54)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
CES1
NM_001025195.2 missense
NM_001025195.2 missense
Scores
1
9
7
Clinical Significance
Conservation
PhyloP100: 3.79
Genes affected
CES1 (HGNC:1863): (carboxylesterase 1) 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 enzyme is the major liver enzyme and functions in liver drug clearance. Mutations of this gene cause carboxylesterase 1 deficiency. Three transcript variants encoding three different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CES1 | NM_001025195.2 | c.256C>A | p.Pro86Thr | missense_variant | 2/14 | ENST00000360526.8 | |
CES1 | NM_001025194.2 | c.253C>A | p.Pro85Thr | missense_variant | 2/14 | ||
CES1 | NM_001266.5 | c.253C>A | p.Pro85Thr | missense_variant | 2/14 | ||
CES1 | XM_005255774.3 | c.256C>A | p.Pro86Thr | missense_variant | 2/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CES1 | ENST00000360526.8 | c.256C>A | p.Pro86Thr | missense_variant | 2/14 | 1 | NM_001025195.2 | P4 |
Frequencies
GnomAD3 genomes Cov.: 54
GnomAD3 genomes
Cov.:
54
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251468Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135906
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461856Hom.: 0 Cov.: 68 AF XY: 0.00000550 AC XY: 4AN XY: 727230
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GnomAD4 genome Cov.: 54
GnomAD4 genome
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54
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 17, 2024 | The c.253C>A (p.P85T) alteration is located in exon 2 (coding exon 2) of the CES1 gene. This alteration results from a C to A substitution at nucleotide position 253, causing the proline (P) at amino acid position 85 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;D
Vest4
MutPred
0.64
.;Loss of catalytic residue at P84 (P = 0.0191);Loss of catalytic residue at P84 (P = 0.0191);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at