16-55846578-G-A

Position:

chr16-55846578-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001143685.2(CES5A):c.1601C>T(p.Pro534Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000675 in 1,614,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

CES5A
NM_001143685.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.19

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]

CES5A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010368615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CES5A	NM_001143685.2 linkuse as main transcript	c.1601C>T	p.Pro534Leu	missense_variant	13/13	ENST00000290567.14	NP_001137157.1
CES5A	NM_001190158.1 linkuse as main transcript	c.1688C>T	p.Pro563Leu	missense_variant	14/14		NP_001177087.1
CES5A	NM_145024.3 linkuse as main transcript	c.1451C>T	p.Pro484Leu	missense_variant	12/12		NP_659461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CES5A	ENST00000290567.14 linkuse as main transcript	c.1601C>T	p.Pro534Leu	missense_variant	13/13	1	NM_001143685.2	ENSP00000290567	P2	Q6NT32-1

Frequencies

GnomAD3 genomes

AF:

0.000362

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

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:

0.000959

GnomAD3 exomes

AF:

0.000107

AC:

AN:

251490

Hom.:

AF XY:

0.0000441

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.000145

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.000134

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:

0.00000360

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000368

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.000654

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:

0.000949

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.000514

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

AC:

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

Oct 03, 2022

The c.1688C>T (p.P563L) alteration is located in exon 14 (coding exon 14) of the CES5A gene. This alteration results from a C to T substitution at nucleotide position 1688, causing the proline (P) at amino acid position 563 to be replaced by a leucine (L). 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

Benign

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.0070

DANN

Benign

0.73

DEOGEN2

Benign

0.042

.;.;.;T;T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.16

T;T;T;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.010

T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.27

.;.;.;N;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.7

N;N;N;N;N;.

REVEL

Benign

0.14

Sift

Benign

0.12

T;T;T;T;T;.

Sift4G

Benign

0.18

T;T;T;T;T;T

Polyphen

0.0030, 0.0

.;B;.;B;.;.

Vest4

0.24

MVP

0.11

MPC

0.035

ClinPred

0.017

GERP RS

-11

Varity_R

0.027

gMVP

0.22

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over