1-22005725-G-C

Variant names:

• chr1-22005725-G-C
• NM_005747.5:c.291G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005747.5(CELA3A):​c.291G>C​(p.Glu97Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CELA3A NM_005747.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELA3A	NM_005747.5	c.291G>C	p.Glu97Asp	missense_variant	Exon 4 of 8	ENST00000290122.8	NP_005738.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELA3A	ENST00000290122.8	c.291G>C	p.Glu97Asp	missense_variant	Exon 4 of 8	1	NM_005747.5	ENSP00000290122.3
CELA3A	ENST00000374663.1	n.306G>C		non_coding_transcript_exon_variant	Exon 4 of 4	2
ENSG00000285959	ENST00000650360.1	n.683G>C		non_coding_transcript_exon_variant	Exon 5 of 9
ENSG00000285959	ENST00000648697.1	n.240+181G>C		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 71

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 03, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.291G>C (p.E97D) alteration is located in exon 4 (coding exon 4) of the CELA3A gene. This alteration results from a G to C substitution at nucleotide position 291, causing the glutamic acid (E) at amino acid position 97 to be replaced by an aspartic acid (D). 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	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.036
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.081	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Uncertain	0.47	D
MutationAssessor	Benign	1.9	L
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.49
Sift	Benign	0.035	D
Sift4G	Benign	0.083	T
Polyphen		0.96	D
Vest4		0.37
MutPred		0.46		Loss of disorder (P = 0.1277);
MVP		0.62
MPC		0.12
ClinPred		0.56	D
GERP RS		0.48
Varity_R		0.11
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-22332218;