chr1-22006979-C-T

Variant names:

• chr1-22006979-C-T
• rs200674633
• NM_005747.5:c.464C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005747.5(CELA3A):​c.464C>T​(p.Thr155Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,612,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: CELA3A NM_005747.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0660
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38182575).

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.464C>T	p.Thr155Ile	missense	Exon 5 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.464C>T	p.Thr155Ile	missense	Exon 5 of 8	ENSP00000290122.3	P09093
	ENSG00000285959	ENST00000648697.1		n.240+1435C>T		intron	N/A
	ENSG00000285959	ENST00000650360.1		n.755-394C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000264 AC: 4 AN: 151318 Hom.: 0 Cov.: 31

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: 0.0000589

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251234 AF XY: 0.0000147

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: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461082 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 726848

African (AFR) AF: 0.00 AC: 0 AN: 33350

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39580

South Asian (SAS) AF: 0.00 AC: 0 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111554

Other (OTH) AF: 0.0000331 AC: 2 AN: 60360

GnomAD4 genome AF: 0.0000264 AC: 4 AN: 151318 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 73892

African (AFR) AF: 0.00 AC: 0 AN: 40866

American (AMR) AF: 0.00 AC: 0 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67944

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.0000264

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.052	N
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.38	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.066
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.38
Sift	Benign	0.23	T
Sift4G	Benign	0.30	T
Polyphen		0.83	P
Vest4		0.33
MutPred		0.59		Loss of phosphorylation at T155 (P = 0.0657)
MVP		0.63
MPC		0.36
ClinPred		0.30	T
GERP RS		-1.1
PromoterAI		-0.030	Neutral
Varity_R		0.14
gMVP		0.52
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs200674633; hg19: chr1-22333472;