7-29030704-C-G

Variant names:

• chr7-29030704-C-G
• rs1052200
• NM_031311.5:c.1193G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_031311.5(CPVL):​c.1193G>C​(p.Arg398Pro) 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 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: CPVL NM_031311.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 30 publications found

Genes affected

CPVL (HGNC:14399): (carboxypeptidase vitellogenic like) The protein encoded by this gene is a carboxypeptidase and bears strong sequence similarity to serine carboxypeptidases. Carboxypeptidases are a large class of proteases that act to cleave a single amino acid from the carboxy termini of proteins or peptides. The exact function of this protein, however, has not been determined. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.9

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPVL	NM_031311.5	c.1193G>C	p.Arg398Pro	missense_variant	Exon 12 of 13	ENST00000265394.10	NP_112601.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPVL	ENST00000265394.10	c.1193G>C	p.Arg398Pro	missense_variant	Exon 12 of 13	1	NM_031311.5	ENSP00000265394.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.64	D;D;.;D
Eigen	Benign	0.15
Eigen_PC	Benign	0.013
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.74	.;.;T;T
M_CAP	Benign	0.083	D
MetaRNN	Pathogenic	0.90	D;D;D;D
MetaSVM	Benign	-0.61	T
MutationAssessor	Pathogenic	3.4	M;M;.;M
PhyloP100		1.1
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.6	D;D;D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.026	D;D;D;D
Sift4G	Uncertain	0.046	D;D;T;D
Polyphen		1.0	D;D;.;D
Vest4		0.75
MutPred		0.72		Loss of MoRF binding (P = 0.0734);Loss of MoRF binding (P = 0.0734);.;Loss of MoRF binding (P = 0.0734);
MVP		0.62
MPC		1.0
ClinPred		0.99	D
GERP RS		2.0
Varity_R		0.93
gMVP		0.88
Mutation Taster		=65/35	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: rs1052200; hg19: chr7-29070320;