Variant chr7-130299348-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016352.4(CPA4):c.229A>G(p.Lys77Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CPA4
NM_016352.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.48

Variant links:

Genes affected

CPA4 (HGNC:15740): (carboxypeptidase A4) This gene is a member of the carboxypeptidase A/B subfamily, and it is located in a cluster with three other family members on chromosome 7. Carboxypeptidases are zinc-containing exopeptidases that catalyze the release of carboxy-terminal amino acids, and are synthesized as zymogens that are activated by proteolytic cleavage. This gene could be involved in the histone hyperacetylation pathway. It is imprinted and may be a strong candidate gene for prostate cancer aggressiveness. [provided by RefSeq, Jul 2008]

CPA4 links:

CPA4 (HGNC:):

CPA4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2660005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPA4	NM_016352.4 linkuse as main transcript	c.229A>G	p.Lys77Glu	missense_variant	3/11	ENST00000222482.10	NP_057436.2	Q9UI42-1A4D1M3
CPA4	XM_047420438.1 linkuse as main transcript	c.-84A>G		5_prime_UTR_premature_start_codon_gain_variant	3/11		XP_047276394.1
CPA4	NM_001163446.2 linkuse as main transcript	c.229A>G	p.Lys77Glu	missense_variant	3/10		NP_001156918.1	Q9UI42-2
CPA4	XM_047420438.1 linkuse as main transcript	c.-84A>G		5_prime_UTR_variant	3/11		XP_047276394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPA4	ENST00000222482.10 linkuse as main transcript	c.229A>G	p.Lys77Glu	missense_variant	3/11	1	NM_016352.4	ENSP00000222482.4		Q9UI42-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251468

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135904

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:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461582

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

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

May 14, 2024

The c.229A>G (p.K77E) alteration is located in exon 3 (coding exon 3) of the CPA4 gene. This alteration results from a A to G substitution at nucleotide position 229, causing the lysine (K) at amino acid position 77 to be replaced by a glutamic acid (E). 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

-0.28

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.11

T;.;.;.;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.59

.;T;T;T;T

M_CAP

Benign

0.0096

MetaRNN

Benign

0.27

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;.;.;M

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.5

.;D;D;D;D

REVEL

Benign

0.13

Sift

Benign

0.29

.;T;D;D;T

Sift4G

Benign

0.21

.;T;D;D;T

Polyphen

0.092

B;.;.;.;B

Vest4

0.29, 0.25

MutPred

0.57

Loss of catalytic residue at K77 (P = 0.066);Loss of catalytic residue at K77 (P = 0.066);Loss of catalytic residue at K77 (P = 0.066);Loss of catalytic residue at K77 (P = 0.066);Loss of catalytic residue at K77 (P = 0.066);

MVP

0.36

MPC

0.22

ClinPred

0.52

GERP RS

5.0

Varity_R

0.72

gMVP

0.61

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