Variant chr7-130310850-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016352.4(CPA4):c.857T>C(p.Val286Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,614,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

CPA4
NM_016352.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.170

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17502952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CPA4	NM_016352.4 linkuse as main transcript	c.857T>C	p.Val286Ala	missense_variant	9/11	ENST00000222482.10	NP_057436.2
CPA4	NM_001163446.2 linkuse as main transcript	c.758T>C	p.Val253Ala	missense_variant	8/10		NP_001156918.1
CPA4	XM_047420438.1 linkuse as main transcript	c.545T>C	p.Val182Ala	missense_variant	9/11		XP_047276394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPA4	ENST00000222482.10 linkuse as main transcript	c.857T>C	p.Val286Ala	missense_variant	9/11	1	NM_016352.4	ENSP00000222482	P1	Q9UI42-1
CPA4	ENST00000445470.6 linkuse as main transcript	c.758T>C	p.Val253Ala	missense_variant	8/10	2		ENSP00000412947		Q9UI42-2
CPA4	ENST00000493259.5 linkuse as main transcript	c.545T>C	p.Val182Ala	missense_variant	7/9	2		ENSP00000419660
CPA4	ENST00000488025.1 linkuse as main transcript	n.330T>C		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251480

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135912

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:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000146

AC:

214

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

727244

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:

0.000183

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000491

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Apr 13, 2022

The c.857T>C (p.V286A) alteration is located in exon 9 (coding exon 9) of the CPA4 gene. This alteration results from a T to C substitution at nucleotide position 857, causing the valine (V) at amino acid position 286 to be replaced by an alanine (A). 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

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.044

T;.;T;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.82

.;T;T;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;.;.;L

MutationTaster

Benign

0.95

N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.9

.;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.33

.;T;T;T

Sift4G

Benign

0.71

.;T;T;T

Polyphen

0.98

D;.;.;D

Vest4

0.32, 0.28, 0.29

MVP

0.32

MPC

0.58

ClinPred

0.42

GERP RS

4.9

Varity_R

0.44

gMVP

0.47

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