16-55849626-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001143685.2(CES5A):ā€‹c.1421T>Cā€‹(p.Phe474Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000068 ( 0 hom. )

Consequence

CES5A
NM_001143685.2 missense, splice_region

Scores

4
15
Splicing: ADA: 0.02582
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66
Variant links:
Genes affected
CES5A (HGNC:26459): (carboxylesterase 5A) 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 also participate in fatty acyl and cholesterol ester metabolism, and may play a role in the blood-brain barrier system. This gene, also called CES5, is predominantly expressed in peripheral tissues, including brain, kidney, lung and testis. It encodes a secreted enzyme. Because of high levels in the urine of male domestic cats, this enzyme is also called cauxin (carboxylesterase-like urinary excreted protein). The enzyme functions in regulating the production of a pheromone precursor and may contribute to lipid and cholesterol transfer processes within male reproductive fluids. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.10605571).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CES5ANM_001143685.2 linkuse as main transcriptc.1421T>C p.Phe474Ser missense_variant, splice_region_variant 11/13 ENST00000290567.14 NP_001137157.1 Q6NT32-1
CES5ANM_001190158.1 linkuse as main transcriptc.1508T>C p.Phe503Ser missense_variant, splice_region_variant 12/14 NP_001177087.1 Q6NT32-4
CES5ANM_145024.3 linkuse as main transcriptc.1274-2786T>C intron_variant NP_659461.1 Q6NT32-2V9HWK3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CES5AENST00000290567.14 linkuse as main transcriptc.1421T>C p.Phe474Ser missense_variant, splice_region_variant 11/131 NM_001143685.2 ENSP00000290567.9 Q6NT32-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152166
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000362
AC:
9
AN:
248692
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
135130
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000261
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
0.00000684
AC:
10
AN:
1461640
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727090
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152166
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000793
ExAC
AF:
0.0000166
AC:
2

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 submitterclinical testingAmbry GeneticsAug 02, 2022The c.1508T>C (p.F503S) alteration is located in exon 12 (coding exon 12) of the CES5A gene. This alteration results from a T to C substitution at nucleotide position 1508, causing the phenylalanine (F) at amino acid position 503 to be replaced by a serine (S). 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
Uncertain
0.52
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.046
.;.;T;T;T
Eigen
Benign
-0.12
Eigen_PC
Benign
-0.13
FATHMM_MKL
Benign
0.46
N
LIST_S2
Benign
0.77
T;T;T;T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.11
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.47
.;.;N;.;.
MutationTaster
Benign
0.63
D;D;D;D;D
PrimateAI
Uncertain
0.49
T
PROVEAN
Uncertain
-2.5
N;N;N;N;.
REVEL
Benign
0.14
Sift
Benign
0.12
T;T;T;T;.
Sift4G
Benign
0.34
T;T;T;T;T
Polyphen
0.81
.;.;P;.;.
Vest4
0.24
MutPred
0.47
.;.;Gain of disorder (P = 0.0058);.;.;
MVP
0.12
MPC
0.31
ClinPred
0.27
T
GERP RS
3.3
Varity_R
0.14
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.026
dbscSNV1_RF
Benign
0.25
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs780022647; hg19: chr16-55883538; API