17-30385115-G-T

Position:

• chr17-30385115-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001304.5(CPD):​c.873G>T​(p.Leu291Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPD NM_001304.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.54

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.814

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPD	NM_001304.5	c.873G>T	p.Leu291Phe	missense_variant	2/21	ENST00000225719.9	NP_001295.2
CPD	NM_001199775.1	c.132G>T	p.Leu44Phe	missense_variant	2/21		NP_001186704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPD	ENST00000225719.9	c.873G>T	p.Leu291Phe	missense_variant	2/21	1	NM_001304.5	ENSP00000225719.4
CPD	ENST00000543464.6	c.132G>T	p.Leu44Phe	missense_variant	2/21	2		ENSP00000444443.2
CPD	ENST00000583275.1	n.238G>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

The c.873G>T (p.L291F) alteration is located in exon 2 (coding exon 2) of the CPD gene. This alteration results from a G to T substitution at nucleotide position 873, causing the leucine (L) at amino acid position 291 to be replaced by a phenylalanine (F). 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	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.078	T;.
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Pathogenic	3.8	H;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		1.0	D;.
Vest4		0.81
MutPred		0.68		Gain of methylation at K289 (P = 0.1124);.;
MVP		0.45
MPC		0.93
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.62
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-28712133;