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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPD	NM_001304.5	MANE Select	c.685C>G	p.Pro229Ala	missense	Exon 1 of 21	NP_001295.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPD	ENST00000225719.9	TSL:1 MANE Select	c.685C>G	p.Pro229Ala	missense	Exon 1 of 21	ENSP00000225719.4	O75976-1
	CPD	ENST00000892708.1		c.685C>G	p.Pro229Ala	missense	Exon 1 of 20	ENSP00000562767.1
	CPD	ENST00000961764.1		c.685C>G	p.Pro229Ala	missense	Exon 1 of 19	ENSP00000631823.1

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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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;