dbSNP rs1460795208: CPD:p.Asn172Thr (chr17-30379495-A-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_001304.5(CPD):c.515A>C(p.Asn172Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,421,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N172S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

CPD
NM_001304.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.79

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity CBPD_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4081894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPD	NM_001304.5 link	c.515A>C	p.Asn172Thr	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.515A>C	p.Asn172Thr	missense_variant	Exon 1 of 21	1	NM_001304.5	ENSP00000225719.4		O75976-1
CPD	ENST00000583275.1 link	n.-121A>C		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

192852

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000155

AC:

AN:

1421292

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

706726

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29226

American (AMR)

AF:

0.00

AC:

AN:

40728

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24710

East Asian (EAS)

AF:

0.00

AC:

AN:

35294

South Asian (SAS)

AF:

0.00

AC:

AN:

82920

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5654

European-Non Finnish (NFE)

AF:

0.0000191

AC:

AN:

1096904

Other (OTH)

AF:

0.0000171

AC:

AN:

58508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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

Feb 27, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.515A>C (p.N172T) alteration is located in exon 1 (coding exon 1) of the CPD gene. This alteration results from a A to C substitution at nucleotide position 515, causing the asparagine (N) at amino acid position 172 to be replaced by a threonine (T). 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

0.53

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.040

Eigen

Benign

0.068

Eigen_PC

Benign

0.042

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.68

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.4

PhyloP100

2.8

PrimateAI

Pathogenic

0.95

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.11

Sift

Benign

0.26

Sift4G

Uncertain

0.0070

Polyphen

0.77

Vest4

0.41

MutPred

0.52

Loss of stability (P = 0.0788);

MVP

0.44

MPC

0.80

ClinPred

0.97

GERP RS

3.2

Varity_R

0.25

gMVP

0.59

Mutation Taster

=57/43

polymorphism

(source)

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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rs1460795208

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