Variant 7-130310925-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_016352.4(CPA4):c.932C>T(p.Ser311Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,614,022 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 2 hom. )

Consequence

CPA4
NM_016352.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.79

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 Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.805

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPA4	NM_016352.4 linkuse as main transcript	c.932C>T	p.Ser311Leu	missense_variant	9/11	ENST00000222482.10	NP_057436.2	Q9UI42-1A4D1M3
CPA4	NM_001163446.2 linkuse as main transcript	c.833C>T	p.Ser278Leu	missense_variant	8/10		NP_001156918.1	Q9UI42-2
CPA4	XM_047420438.1 linkuse as main transcript	c.620C>T	p.Ser207Leu	missense_variant	9/11		XP_047276394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CPA4	ENST00000222482.10 linkuse as main transcript	c.932C>T	p.Ser311Leu	missense_variant	9/11	1	NM_016352.4	ENSP00000222482.4	Q9UI42-1
CPA4	ENST00000445470.6 linkuse as main transcript	c.833C>T	p.Ser278Leu	missense_variant	8/10	2		ENSP00000412947.2	Q9UI42-2
CPA4	ENST00000493259.5 linkuse as main transcript	c.620C>T	p.Ser207Leu	missense_variant	7/9	2		ENSP00000419660.1	B7Z5J4
CPA4	ENST00000488025.1 linkuse as main transcript	n.405C>T		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000795

AC:

AN:

251452

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000506

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000966

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000494

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 30, 2023

The c.932C>T (p.S311L) alteration is located in exon 9 (coding exon 9) of the CPA4 gene. This alteration results from a C to T substitution at nucleotide position 932, causing the serine (S) at amino acid position 311 to be replaced by a leucine (L). 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

Uncertain

0.47

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.;T;T

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

.;D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.80

D;D;D;D

MetaSVM

Benign

-0.51

MutationAssessor

Pathogenic

3.5

H;.;.;H

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-5.8

.;D;D;D

REVEL

Pathogenic

0.65

Sift

Pathogenic

0.0

.;D;D;D

Sift4G

Pathogenic

0.0010

.;D;D;D

Polyphen

1.0

D;.;.;D

Vest4

0.84, 0.88, 0.85

MVP

0.59

MPC

0.52

ClinPred

0.80

GERP RS

5.0

Varity_R

0.96

gMVP

0.76

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