1-22007391-A-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005747.5(CELA3A):c.518A>C(p.Asp173Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000577 in 1,611,814 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D173E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00036 ( 3 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 1 hom. )

Consequence

CELA3A
NM_005747.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23

Variant links:

Genes affected

CELA3A (HGNC:15944): (chymotrypsin like elastase 3A) 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 3A has little elastolytic activity. Like most of the human elastases, elastase 3A 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 3A preferentially cleaves proteins after alanine residues. Elastase 3A 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. [provided by RefSeq, Jul 2008]

CELA3A links:

ENSG00000285959 (HGNC:):

ENSG00000285959 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019827873).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELA3A	NM_005747.5 link	c.518A>C	p.Asp173Ala	missense_variant	Exon 6 of 8	ENST00000290122.8	NP_005738.4	P09093

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CELA3A	ENST00000290122.8 link	c.518A>C	p.Asp173Ala	missense_variant	Exon 6 of 8	1	NM_005747.5	ENSP00000290122.3	P09093
ENSG00000285959	ENST00000650360.1 link	n.773A>C		non_coding_transcript_exon_variant	Exon 6 of 9
ENSG00000285959	ENST00000648697.1 link	n.240+1847A>C		intron_variant	Intron 1 of 3
CELA3A	ENST00000400271.2 link	c.-59A>C		upstream_gene_variant		3		ENSP00000383130.2	B1AQ55

Frequencies

GnomAD3 genomes

AF:

0.000363

AC:

AN:

151452

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

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:

0.000480

GnomAD3 exomes

AF:

0.0000879

AC:

AN:

250292

Hom.:

AF XY:

0.0000813

AC XY:

AN XY:

135314

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.0000290

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:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1460242

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

726438

show subpopulations

Gnomad4 AFR exome

AF:

0.000961

Gnomad4 AMR exome

AF:

0.0000224

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000363

AC:

AN:

151572

Hom.:

Cov.:

AF XY:

0.000459

AC XY:

AN XY:

74106

show subpopulations

Gnomad4 AFR

AF:

0.00129

Gnomad4 AMR

AF:

0.0000656

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:

0.000475

Alfa

AF:

0.0000513

Hom.:

Bravo

AF:

0.000412

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

Mar 29, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.518A>C (p.D173A) alteration is located in exon 6 (coding exon 6) of the CELA3A gene. This alteration results from a A to C substitution at nucleotide position 518, causing the aspartic acid (D) at amino acid position 173 to be replaced by an alanine (A). 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

0.20

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Uncertain

0.45

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.77

M_CAP

Benign

0.029

MetaRNN

Benign

0.020

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.5

PROVEAN

Pathogenic

-6.8

REVEL

Benign

0.19

Sift

Benign

0.30

Sift4G

Benign

0.35

Polyphen

0.019

Vest4

0.20

MVP

0.52

MPC

0.38

ClinPred

0.080

GERP RS

2.4

Varity_R

0.25

gMVP

0.68

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