17-30379207-T-G

Variant names:

• chr17-30379207-T-G
• rs1041634728
• NM_001304.5:c.227T>G

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.227T>G​(p.Leu76Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPD NM_001304.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.180
• 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=0.06785619).

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.227T>G	p.Leu76Arg	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.227T>G	p.Leu76Arg	missense	Exon 1 of 21	ENSP00000225719.4	O75976-1
	CPD	ENST00000892708.1		c.227T>G	p.Leu76Arg	missense	Exon 1 of 20	ENSP00000562767.1
	CPD	ENST00000961764.1		c.227T>G	p.Leu76Arg	missense	Exon 1 of 19	ENSP00000631823.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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	0.081
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.18
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.052
Sift	Benign	0.13	T
Sift4G	Uncertain	0.014	D
Polyphen		0.0	B
Vest4		0.22
MutPred		0.69		Gain of MoRF binding (P = 0.0107)
MVP		0.18
MPC		1.5
ClinPred		0.078	T
GERP RS		2.4
PromoterAI		-0.16	Neutral
Varity_R		0.12
gMVP		0.66

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: rs1041634728; hg19: chr17-28706225;