17-30379665-C-G

Variant names:

• chr17-30379665-C-G
• rs530282755
• NM_001304.5:c.685C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001304.5(CPD):​c.685C>G​(p.Pro229Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000717 in 1,521,694 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. P229T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00051 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00074 (2 hom.)
• Consequence: CPD NM_001304.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.42
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014585882).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPD	NM_001304.5	c.685C>G	p.Pro229Ala	missense_variant	Exon 1 of 21	ENST00000225719.9	NP_001295.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPD	ENST00000225719.9	c.685C>G	p.Pro229Ala	missense_variant	Exon 1 of 21	1	NM_001304.5	ENSP00000225719.4
CPD	ENST00000583275.1	n.50C>G		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.000506 AC: 77 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000537 AC: 76 AN: 141480 AF XY: 0.000506

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000923

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000701

Gnomad NFE exome AF: 0.000717

Gnomad OTH exome AF: 0.000969

GnomAD4 exome AF: 0.000740 AC: 1014 AN: 1369470 Hom.: 2 Cov.: 33 AF XY: 0.000703 AC XY: 479 AN XY: 681324

African (AFR) AF: 0.00 AC: 0 AN: 26784

American (AMR) AF: 0.000943 AC: 26 AN: 27578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22768

East Asian (EAS) AF: 0.00 AC: 0 AN: 33564

South Asian (SAS) AF: 0.00 AC: 0 AN: 76854

European-Finnish (FIN) AF: 0.000574 AC: 21 AN: 36566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5462

European-Non Finnish (NFE) AF: 0.000871 AC: 944 AN: 1083368

Other (OTH) AF: 0.000407 AC: 23 AN: 56526

GnomAD4 genome AF: 0.000506 AC: 77 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.000497 AC XY: 37 AN XY: 74434

African (AFR) AF: 0.000144 AC: 6 AN: 41542

American (AMR) AF: 0.00118 AC: 18 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000721 AC: 49 AN: 68002

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000638

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00130 AC: 5

ExAC AF: 0.000365 AC: 42

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.685C>G (p.P229A) alteration is located in exon 1 (coding exon 1) of the CPD gene. This alteration results from a C to G substitution at nucleotide position 685, causing the proline (P) at amino acid position 229 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	0.062
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Benign	0.86
DEOGEN2	Benign	0.0024	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.051
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.4
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.12
Sift	Benign	0.52	T
Sift4G	Benign	0.85	T
Polyphen		1.0	D
Vest4		0.20
MVP		0.37
MPC		0.34
ClinPred		0.050	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.043
gMVP		0.43
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs530282755; hg19: chr17-28706683;