Genetic Variant NM_001304.5:c.41G>A (chr17-30379021-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001304.5(CPD):c.41G>A(p.Gly14Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,404,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CPD
NM_001304.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.183

Publications

0 publications found

Variant links:

Genes affected

CPD (HGNC:2301): (carboxypeptidase D) The metallocarboxypeptidase family of enzymes is divided into 2 subfamilies based on sequence similarities. The pancreatic carboxypeptidase-like and the regulatory B-type carboxypeptidase subfamilies. Carboxypeptidase D has been identified as a regulatory B-type carboxypeptidase. CPD is a homolog of duck gp180, a hepatitis B virus-binding protein. Transcript variants utilizing alternative polyadenylation signals exist for this gene. [provided by RefSeq, Jul 2008]

CPD links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.115151405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPD	NM_001304.5 link	c.41G>A	p.Gly14Glu	missense_variant	Exon 1 of 21	ENST00000225719.9	NP_001295.2	O75976-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPD	ENST00000225719.9 link	c.41G>A	p.Gly14Glu	missense_variant	Exon 1 of 21	1	NM_001304.5	ENSP00000225719.4		O75976-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000214

AC:

AN:

1404782

Hom.:

Cov.:

AF XY:

0.00000287

AC XY:

AN XY:

697648

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29066

American (AMR)

AF:

0.00

AC:

AN:

39990

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24606

East Asian (EAS)

AF:

0.00

AC:

AN:

34032

South Asian (SAS)

AF:

0.0000123

AC:

AN:

81536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39674

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5412

European-Non Finnish (NFE)

AF:

9.16e-7

AC:

AN:

1092226

Other (OTH)

AF:

0.0000172

AC:

AN:

58240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Jan 21, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.41G>A (p.G14E) alteration is located in exon 1 (coding exon 1) of the CPD gene. This alteration results from a G to A substitution at nucleotide position 41, causing the glycine (G) at amino acid position 14 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

0.13

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.00097

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.47

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

PhyloP100

0.18

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.33

REVEL

Benign

0.029

Sift

Benign

0.10

Sift4G

Benign

0.60

Polyphen

0.0

Vest4

0.17

MutPred

0.39

Loss of MoRF binding (P = 0.0313);

MVP

0.33

MPC

1.3

ClinPred

0.086

GERP RS

0.92

PromoterAI

0.012

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.096

gMVP

0.54

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

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NM_001304.5:c.41G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over