17-30378993-C-T

Variant names:

• chr17-30378993-C-T
• rs181199485
• NM_001304.5:c.13C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001304.5(CPD):​c.13C>T​(p.Arg5Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,388,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R5R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CPD NM_001304.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.84
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030736566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPD	NM_001304.5	c.13C>T	p.Arg5Trp	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.13C>T	p.Arg5Trp	missense_variant	Exon 1 of 21	1	NM_001304.5	ENSP00000225719.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1388058 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 688760

African (AFR) AF: 0.00 AC: 0 AN: 28374

American (AMR) AF: 0.00 AC: 0 AN: 37084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23978

East Asian (EAS) AF: 0.00 AC: 0 AN: 33178

South Asian (SAS) AF: 0.00 AC: 0 AN: 80026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4862

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1085946

Other (OTH) AF: 0.00 AC: 0 AN: 57520

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.6
DANN	Benign	0.81
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-2.8
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.026
Sift	Benign	0.083	T
Sift4G	Benign	0.067	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.21		Loss of disorder (P = 0.0067);
MVP		0.12
MPC		1.2
ClinPred		0.37	T
GERP RS		-8.7
PromoterAI		-0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.043
gMVP		0.52
Mutation Taster		=91/9	polymorphism

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: rs181199485; hg19: chr17-28706011;