16-55856381-A-G

Position:

• chr16-55856381-A-G

Variant summary

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

The NM_001143685.2(CES5A):​c.1121T>C​(p.Ile374Thr) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CES5A NM_001143685.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.442

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]

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=0.23490632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CES5A	NM_001143685.2	c.1121T>C	p.Ile374Thr	missense_variant	9/13	ENST00000290567.14	NP_001137157.1
CES5A	NM_001190158.1	c.1208T>C	p.Ile403Thr	missense_variant	10/14		NP_001177087.1
CES5A	NM_145024.3	c.1121T>C	p.Ile374Thr	missense_variant	9/12		NP_659461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CES5A	ENST00000290567.14	c.1121T>C	p.Ile374Thr	missense_variant	9/13	1	NM_001143685.2	ENSP00000290567	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 27, 2022

The c.1208T>C (p.I403T) alteration is located in exon 10 (coding exon 10) of the CES5A gene. This alteration results from a T to C substitution at nucleotide position 1208, causing the isoleucine (I) at amino acid position 403 to be replaced by a threonine (T). 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	0.18
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.7
DANN	Benign	0.66
DEOGEN2	Benign	0.066	.;.;.;T;T;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.53	T;T;T;T;T;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.23	T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.23	.;N;.;N;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.2	N;N;N;N;N;.
REVEL	Benign	0.14
Sift	Benign	0.30	T;T;T;T;T;.
Sift4G	Benign	0.25	T;T;T;T;T;T
Polyphen		0.45, 0.27	.;B;.;B;.;.
Vest4		0.26
MutPred		0.57		.;Loss of stability (P = 0.0107);.;Loss of stability (P = 0.0107);.;.;
MVP		0.19
MPC		0.060
ClinPred		0.36	T
GERP RS		3.2
Varity_R		0.063
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr16-55890293;