Variant chr7-130367392-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_080385.5(CPA5):c.859C>T(p.Pro287Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,613,968 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

CPA5
NM_080385.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13

Variant links:

Genes affected

CPA5 (HGNC:15722): (carboxypeptidase A5) Carboxypeptidases have functions ranging from digestion of food to selective biosynthesis of neuroendocrine peptides. Members of the A/B subfamily of carboxypeptidases, such as CPA5, contain an approximately 90-amino acid pro region that assists in the folding of the active carboxypeptidase domain. Cleavage of the pro region activates the enzyme (Wei et al., 2002 [PubMed 11836249]).[supplied by OMIM, Mar 2008]

CPA5 links:

CPA5 (HGNC:):

CPA5 links:

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ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
CPA5	NM_080385.5 linkuse as main transcript	c.859C>T	p.Pro287Ser	missense_variant	11/13	ENST00000474905.6	NP_525124.3	Q8WXQ8-1A4D1M2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPA5	ENST00000474905.6 linkuse as main transcript	c.859C>T	p.Pro287Ser	missense_variant	11/13	1	NM_080385.5	ENSP00000417314.1		Q8WXQ8-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152118

Hom.:

Cov.:

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251242

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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 submitter

clinical testing

Ambry Genetics

Aug 14, 2023

The c.859C>T (p.P287S) alteration is located in exon 12 (coding exon 9) of the CPA5 gene. This alteration results from a C to T substitution at nucleotide position 859, causing the proline (P) at amino acid position 287 to be replaced by a serine (S). 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

Benign

0.20

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;T;T;.;T;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

.;.;.;D;.;D

M_CAP

Benign

0.0094

MetaRNN

Uncertain

0.69

D;D;D;D;D;D

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.1

M;M;M;M;M;M

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-6.8

D;D;D;D;D;D

REVEL

Benign

0.24

Sift

Uncertain

0.029

D;D;D;D;D;D

Sift4G

Benign

0.096

T;T;T;D;T;T

Polyphen

0.77

P;P;P;.;P;P

Vest4

0.81

MVP

0.58

MPC

0.35

ClinPred

0.50

GERP RS

4.9

Varity_R

0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over