3-148879842-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001870.4(CPA3):​c.529G>A​(p.Ala177Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000026 in 1,612,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

CPA3
NM_001870.4 missense

Scores

8
7
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.54
Variant links:
Genes affected
CPA3 (HGNC:2298): (carboxypeptidase A3) This gene encodes a member of the carboxypeptidase A family of zinc metalloproteases. The encoded preproprotein is proteolytically processed to generate a mature protease that is released by mast cells and may be involved in the degradation of endogenous proteins and the inactivation of venom-associated peptides. Expression of this gene may be elevated in human asthma patients. [provided by RefSeq, Nov 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.84

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CPA3NM_001870.4 linkc.529G>A p.Ala177Thr missense_variant 6/11 ENST00000296046.4 NP_001861.2 P15088

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CPA3ENST00000296046.4 linkc.529G>A p.Ala177Thr missense_variant 6/111 NM_001870.4 ENSP00000296046.3 P15088
ENSG00000240521ENST00000488190.1 linkn.163-9753C>T intron_variant 1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000359
AC:
9
AN:
251012
Hom.:
0
AF XY:
0.0000369
AC XY:
5
AN XY:
135632
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000247
AC:
36
AN:
1460334
Hom.:
0
Cov.:
30
AF XY:
0.0000234
AC XY:
17
AN XY:
726580
show subpopulations
Gnomad4 AFR exome
AF:
0.0000599
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000261
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152284
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000386
Hom.:
0
Bravo
AF:
0.0000340
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 18, 2024The c.529G>A (p.A177T) alteration is located in exon 6 (coding exon 6) of the CPA3 gene. This alteration results from a G to A substitution at nucleotide position 529, causing the alanine (A) at amino acid position 177 to be replaced by a threonine (T). 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
0.72
BayesDel_addAF
Uncertain
0.056
T
BayesDel_noAF
Uncertain
0.020
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.39
T
Eigen
Pathogenic
0.99
Eigen_PC
Pathogenic
0.88
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Pathogenic
0.97
D
M_CAP
Benign
0.045
D
MetaRNN
Pathogenic
0.84
D
MetaSVM
Benign
-0.35
T
MutationAssessor
Pathogenic
4.0
H
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-4.0
D
REVEL
Uncertain
0.52
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.66
MVP
0.73
MPC
0.15
ClinPred
0.99
D
GERP RS
4.8
Varity_R
0.92
gMVP
0.92

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.17
Details are displayed if max score is > 0.2

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: rs192487183; hg19: chr3-148597629; COSMIC: COSV56045218; COSMIC: COSV56045218; API