chr1-22003041-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_005747.5(CELA3A):​c.82C>A​(p.Arg28Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000719 in 139,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R28C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000072 ( 0 hom., cov: 27)

Consequence

CELA3A
NM_005747.5 missense

Scores

6
6
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.117
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.807

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CELA3ANM_005747.5 linkc.82C>A p.Arg28Ser missense_variant Exon 2 of 8 ENST00000290122.8 NP_005738.4 P09093

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CELA3AENST00000290122.8 linkc.82C>A p.Arg28Ser missense_variant Exon 2 of 8 1 NM_005747.5 ENSP00000290122.3 P09093
CELA3AENST00000374663.1 linkn.97C>A non_coding_transcript_exon_variant Exon 2 of 4 2
ENSG00000285959ENST00000650360.1 linkn.522-2406C>A intron_variant Intron 3 of 8

Frequencies

GnomAD3 genomes
AF:
0.00000719
AC:
1
AN:
139008
Hom.:
0
Cov.:
27
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:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000149
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000719
AC:
1
AN:
139008
Hom.:
0
Cov.:
27
AF XY:
0.00
AC XY:
0
AN XY:
67734
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:
0.0000149
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.83
BayesDel_addAF
Pathogenic
0.16
D
BayesDel_noAF
Uncertain
0.0
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.22
T
Eigen
Benign
0.068
Eigen_PC
Benign
-0.16
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.63
T
M_CAP
Uncertain
0.093
D
MetaRNN
Pathogenic
0.81
D
MetaSVM
Uncertain
0.37
D
MutationAssessor
Uncertain
2.8
M
PROVEAN
Pathogenic
-5.3
D
REVEL
Uncertain
0.36
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.64
MutPred
0.61
Gain of glycosylation at R28 (P = 0.0074);
MVP
0.87
MPC
0.48
ClinPred
0.98
D
GERP RS
2.4
Varity_R
0.84
gMVP
0.88

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.21
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.21
Position offset: 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.

Other links and lift over

dbSNP: rs545148620; hg19: chr1-22329534; API