dbSNP rs144477023: CELA3A:p.Gly19Ser (chr1-22003014-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_005747.5(CELA3A):c.55G>A(p.Gly19Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000355 in 1,575,854 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000036 ( 5 hom. )

Consequence

CELA3A
NM_005747.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.54

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005747.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELA3A	NM_005747.5	MANE Select	c.55G>A	p.Gly19Ser	missense	Exon 2 of 8	NP_005738.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CELA3A	ENST00000290122.8	TSL:1 MANE Select	c.55G>A	p.Gly19Ser	missense	Exon 2 of 8	ENSP00000290122.3	P09093
CELA3A	ENST00000374663.1	TSL:2	n.70G>A		non_coding_transcript_exon	Exon 2 of 4
ENSG00000285959	ENST00000650360.1		n.522-2433G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000281

AC:

AN:

142534

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000287

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000685

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:

0.0000299

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000618

AC:

AN:

242788

AF XY:

0.0000835

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1433320

Hom.:

Cov.:

AF XY:

0.0000378

AC XY:

AN XY:

713484

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25570

American (AMR)

AF:

0.00

AC:

AN:

44128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25872

East Asian (EAS)

AF:

0.00

AC:

AN:

37030

South Asian (SAS)

AF:

0.00

AC:

AN:

84170

European-Finnish (FIN)

AF:

0.0000193

AC:

AN:

51842

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5668

European-Non Finnish (NFE)

AF:

0.0000400

AC:

AN:

1100174

Other (OTH)

AF:

0.000119

AC:

AN:

58866

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000281

AC:

AN:

142534

Hom.:

Cov.:

AF XY:

0.0000144

AC XY:

AN XY:

69466

show subpopulations

African (AFR)

AF:

0.0000287

AC:

AN:

34852

American (AMR)

AF:

0.0000685

AC:

AN:

14598

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3434

East Asian (EAS)

AF:

0.00

AC:

AN:

4774

South Asian (SAS)

AF:

0.00

AC:

AN:

4648

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10052

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000299

AC:

AN:

66992

Other (OTH)

AF:

0.00

AC:

AN:

1964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000859

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000108

AC:

EpiCase

AF:

0.0000551

EpiControl

AF:

0.000120

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.15

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.54

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.49

M_CAP

Benign

0.030

MetaRNN

Benign

0.14

MetaSVM

Uncertain

0.14

MutationAssessor

Benign

1.9

PhyloP100

4.5

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.21

Sift

Benign

0.13

Sift4G

Benign

0.085

Polyphen

0.044

Vest4

0.24

MVP

0.89

MPC

0.083

ClinPred

0.11

GERP RS

2.2

Varity_R

0.095

gMVP

0.74

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.27

Position offset: 26

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over