Variant 7-29072323-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_031311.5(CPVL):c.710A>G(p.Asp237Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CPVL
NM_031311.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.61

Variant links:

Genes affected

CPVL (HGNC:14399): (carboxypeptidase vitellogenic like) The protein encoded by this gene is a carboxypeptidase and bears strong sequence similarity to serine carboxypeptidases. Carboxypeptidases are a large class of proteases that act to cleave a single amino acid from the carboxy termini of proteins or peptides. The exact function of this protein, however, has not been determined. [provided by RefSeq, Jan 2017]

CPVL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPVL	NM_031311.5 linkuse as main transcript	c.710A>G	p.Asp237Gly	missense_variant	8/13	ENST00000265394.10	NP_112601.3	Q9H3G5A0A024RA40

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CPVL	ENST00000265394.10 linkuse as main transcript	c.710A>G	p.Asp237Gly	missense_variant	8/13	1	NM_031311.5	ENSP00000265394.5	Q9H3G5
CPVL	ENST00000396276.7 linkuse as main transcript	c.710A>G	p.Asp237Gly	missense_variant	8/13	1		ENSP00000379572.3	Q9H3G5
CPVL	ENST00000409850.5 linkuse as main transcript	c.710A>G	p.Asp237Gly	missense_variant	12/17	2		ENSP00000387164.1	Q9H3G5
CPVL	ENST00000448959.5 linkuse as main transcript	c.500A>G	p.Asp167Gly	missense_variant	6/8	2		ENSP00000409036.1	C9JLV0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461806

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727202

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 14, 2024

The c.710A>G (p.D237G) alteration is located in exon 8 (coding exon 7) of the CPVL gene. This alteration results from a A to G substitution at nucleotide position 710, causing the aspartic acid (D) at amino acid position 237 to be replaced by a glycine (G). 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

0.41

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.37

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.58

D;D;D;.

Eigen

Pathogenic

0.74

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

.;.;D;D

M_CAP

Uncertain

0.21

MetaRNN

Pathogenic

0.97

D;D;D;D

MetaSVM

Pathogenic

0.90

MutationAssessor

Pathogenic

3.2

M;M;M;.

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-5.1

D;D;D;D

REVEL

Pathogenic

0.94

Sift

Uncertain

0.011

D;D;D;D

Sift4G

Uncertain

0.015

D;D;D;.

Polyphen

1.0

D;D;D;.

Vest4

0.86

MutPred

0.89

Loss of phosphorylation at Y239 (P = 0.0968);Loss of phosphorylation at Y239 (P = 0.0968);Loss of phosphorylation at Y239 (P = 0.0968);.;

MVP

0.97

MPC

0.88

ClinPred

1.0

GERP RS

5.1

Varity_R

0.84

gMVP

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.31

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.31

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over