dbSNP rs149807589: CELA3A:p.Arg210Ser (chr1-22007501-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005747.5(CELA3A):c.628C>A(p.Arg210Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R210C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CELA3A
NM_005747.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.337

Publications

2 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07483381).

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.628C>A	p.Arg210Ser	missense	Exon 6 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.628C>A	p.Arg210Ser	missense	Exon 6 of 8	ENSP00000290122.3	P09093
CELA3A	ENST00000400271.2	TSL:3	c.52C>A	p.Arg18Ser	missense	Exon 1 of 4	ENSP00000383130.2	B1AQ55
ENSG00000285959	ENST00000650360.1		n.883C>A		non_coding_transcript_exon	Exon 6 of 9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249484

AF XY:

0.00000741

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:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458658

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725656

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33190

American (AMR)

AF:

0.00

AC:

AN:

44526

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26044

East Asian (EAS)

AF:

0.00

AC:

AN:

39458

South Asian (SAS)

AF:

0.00

AC:

AN:

85920

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5648

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110310

Other (OTH)

AF:

0.0000166

AC:

AN:

60226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.0056

BayesDel_noAF

Benign

-0.25

CADD

Benign

8.6

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.12

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.69

M_CAP

Benign

0.016

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.80

MutationAssessor

Benign

-0.035

PhyloP100

-0.34

PROVEAN

Benign

-1.1

REVEL

Benign

0.22

Sift

Benign

0.77

Sift4G

Benign

0.74

Polyphen

0.023

Vest4

0.17

MutPred

0.57

Gain of disorder (P = 0.0423)

MVP

0.35

MPC

0.097

ClinPred

0.045

GERP RS

0.56

PromoterAI

-0.082

Neutral

(source)

Varity_R

0.12

gMVP

0.64

Mutation Taster

=92/8

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over