NM_001304.5:c.634C>A

Variant names:

• chr17-30379614-C-A
• rs1451733449
• NM_001304.5:c.634C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001304.5(CPD):​c.634C>A​(p.Arg212Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R212G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CPD NM_001304.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPD	NM_001304.5	c.634C>A	p.Arg212Ser	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.634C>A	p.Arg212Ser	missense_variant	Exon 1 of 21	1	NM_001304.5	ENSP00000225719.4
CPD	ENST00000583275.1	n.-2C>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1316762 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 650722

African (AFR) AF: 0.00 AC: 0 AN: 25066

American (AMR) AF: 0.00 AC: 0 AN: 18800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20956

East Asian (EAS) AF: 0.00 AC: 0 AN: 31446

South Asian (SAS) AF: 0.00 AC: 0 AN: 70862

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4478

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1055582

Other (OTH) AF: 0.00 AC: 0 AN: 54042

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.079	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.4
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.12
Sift	Uncertain	0.017	D
Sift4G	Benign	0.20	T
Polyphen		0.97	D
Vest4		0.59
MutPred		0.54		Gain of phosphorylation at R212 (P = 0.0175);
MVP		0.31
MPC		0.59
ClinPred		0.60	D
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.68

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

Other links and lift over

dbSNP: rs1451733449; hg19: chr17-28706632;