Genetic Variant CELA3B:p.Thr57Ile (chr1-21980864-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_007352.4(CELA3B):c.170C>T(p.Thr57Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000683 in 1,609,368 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 22)

Exomes 𝑓: 0.000073 ( 1 hom. )

Consequence

CELA3B
NM_007352.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.14

Variant links:

Genes affected

CELA3B (HGNC:15945): (chymotrypsin like elastase 3B) Elastases form a subfamily of serine proteases that hydrolyze many proteins in addition to elastin. Humans have six elastase genes which encode the structurally similar proteins elastase 1, 2, 2A, 2B, 3A, and 3B. Unlike other elastases, elastase 3B has little elastolytic activity. Like most of the human elastases, elastase 3B is secreted from the pancreas as a zymogen and, like other serine proteases such as trypsin, chymotrypsin and kallikrein, it has a digestive function in the intestine. Elastase 3B preferentially cleaves proteins after alanine residues. Elastase 3B may also function in the intestinal transport and metabolism of cholesterol. Both elastase 3A and elastase 3B have been referred to as protease E and as elastase 1, and excretion of this protein in fecal material is frequently used as a measure of pancreatic function in clinical assays. [provided by RefSeq, May 2009]

CELA3B links:

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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 rank	MANE	Protein	UniProt
CELA3B	NM_007352.4 link	c.170C>T	p.Thr57Ile	missense_variant	Exon 3 of 8	ENST00000337107.11	NP_031378.1	P08861

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CELA3B	ENST00000337107.11 link	c.170C>T	p.Thr57Ile	missense_variant	Exon 3 of 8	1	NM_007352.4	ENSP00000338369.6	P08861
CELA3B	ENST00000374666.1 link	n.221C>T		non_coding_transcript_exon_variant	Exon 3 of 5	3
CELA3B	ENST00000400277.2 link	c.-238C>T		upstream_gene_variant		5		ENSP00000383135.2	A0A0A0MSA6

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

149744

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000220

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000446

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000204

AC:

AN:

244682

Hom.:

AF XY:

0.0000225

AC XY:

AN XY:

133292

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

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:

0.0000365

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000733

AC:

107

AN:

1459508

Hom.:

Cov.:

AF XY:

0.0000923

AC XY:

AN XY:

726146

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000837

Gnomad4 OTH exome

AF:

0.0000996

GnomAD4 genome

AF:

0.0000200

AC:

AN:

149860

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73134

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000446

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000581

Hom.:

ExAC

AF:

0.0000497

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.170C>T (p.T57I) alteration is located in exon 3 (coding exon 3) of the CELA3B gene. This alteration results from a C to T substitution at nucleotide position 170, causing the threonine (T) at amino acid position 57 to be replaced by an isoleucine (I). 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

0.41

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.054

MetaRNN

Uncertain

0.54

MetaSVM

Uncertain

0.33

MutationAssessor

Benign

-0.62

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.58

Sift

Benign

0.12

Sift4G

Benign

0.32

Polyphen

0.90

Vest4

0.39

MVP

0.39

MPC

0.70

ClinPred

0.69

GERP RS

5.2

Varity_R

0.45

gMVP

0.81

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