1-22003041-C-G

Variant names:

• chr1-22003041-C-G
• rs545148620
• NM_005747.5:c.82C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005747.5(CELA3A):​c.82C>G​(p.Arg28Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CELA3A NM_005747.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 0 publications found

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]

ENSG00000285959 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.836

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.82C>G	p.Arg28Gly	missense	Exon 2 of 8	NP_005738.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELA3A	ENST00000290122.8	TSL:1 MANE Select	c.82C>G	p.Arg28Gly	missense	Exon 2 of 8	ENSP00000290122.3	P09093
	CELA3A	ENST00000374663.1	TSL:2	n.97C>G		non_coding_transcript_exon	Exon 2 of 4
	ENSG00000285959	ENST00000650360.1		n.522-2406C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD2 exomes AF: 0.00 AC: 0 AN: 241594 AF XY: 0.00

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: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1432792 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 713180

African (AFR) AF: 0.00 AC: 0 AN: 25126

American (AMR) AF: 0.00 AC: 0 AN: 44106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25884

East Asian (EAS) AF: 0.00 AC: 0 AN: 36944

South Asian (SAS) AF: 0.00 AC: 0 AN: 83966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100390

Other (OTH) AF: 0.00 AC: 0 AN: 58856

GnomAD4 genome Cov.: 27

ExAC AF: 0.0000169 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.032
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.64	T
M_CAP	Uncertain	0.093	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Uncertain	0.33	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.12
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.67		Loss of stability (P = 0.01)
MVP		0.84
MPC		0.51
ClinPred		0.96	D
GERP RS		2.4
Varity_R		0.76
gMVP		0.89
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs545148620; hg19: chr1-22329534;