16-55849690-C-T

Position:

chr16-55849690-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001143685.2(CES5A):c.1357G>A(p.Asp453Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000366 in 1,613,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

CES5A
NM_001143685.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.23

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:

CES5A (HGNC:):

CES5A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.781

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CES5A	NM_001143685.2 linkuse as main transcript	c.1357G>A	p.Asp453Asn	missense_variant	11/13	ENST00000290567.14	NP_001137157.1	Q6NT32-1
CES5A	NM_001190158.1 linkuse as main transcript	c.1444G>A	p.Asp482Asn	missense_variant	12/14		NP_001177087.1	Q6NT32-4
CES5A	NM_145024.3 linkuse as main transcript	c.1274-2850G>A		intron_variant			NP_659461.1	Q6NT32-2V9HWK3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CES5A	ENST00000290567.14 linkuse as main transcript	c.1357G>A	p.Asp453Asn	missense_variant	11/13	1	NM_001143685.2	ENSP00000290567.9		Q6NT32-1

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000724

AC:

AN:

248770

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135174

show subpopulations

Gnomad AFR exome

AF:

0.000907

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461706

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000184

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000263

Hom.:

Bravo

AF:

0.000159

ExAC

AF:

0.0000581

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

Dec 03, 2021

The c.1444G>A (p.D482N) alteration is located in exon 12 (coding exon 12) of the CES5A gene. This alteration results from a G to A substitution at nucleotide position 1444, causing the aspartic acid (D) at amino acid position 482 to be replaced by an asparagine (N). 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

Pathogenic

0.60

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

.;.;T;T;T

Eigen

Pathogenic

0.75

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

D;D;D;D;D

M_CAP

Benign

0.035

MetaRNN

Pathogenic

0.78

D;D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

.;.;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-4.6

D;D;D;D;.

REVEL

Benign

0.26

Sift

Pathogenic

0.0

D;D;D;D;.

Sift4G

Uncertain

0.0030

D;D;D;D;D

Polyphen

1.0

.;.;D;.;.

Vest4

0.77

MVP

0.11

MPC

0.26

ClinPred

0.74

GERP RS

5.3

Varity_R

0.73

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

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