7-29064087-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031311.5(CPVL):c.1111T>G(p.Leu371Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CPVL NM_031311.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.34

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPVL	NM_031311.5	c.1111T>G	p.Leu371Val	missense_variant	11/13	ENST00000265394.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPVL	ENST00000265394.10	c.1111T>G	p.Leu371Val	missense_variant	11/13	1	NM_031311.5	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

Oct 29, 2021

The c.1111T>G (p.L371V) alteration is located in exon 11 (coding exon 10) of the CPVL gene. This alteration results from a T to G substitution at nucleotide position 1111, causing the leucine (L) at amino acid position 371 to be replaced by a valine (V). 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	Benign	0.19
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.010
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.29	T;T;T
Eigen	Benign	-0.020
Eigen_PC	Benign	0.022
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Uncertain	0.57
Sift	Benign	0.35	T;T;T
Sift4G	Benign	0.39	T;T;T
Polyphen		0.93	P;P;P
Vest4		0.47
MutPred		0.60		Gain of catalytic residue at L371 (P = 0.1388);Gain of catalytic residue at L371 (P = 0.1388);Gain of catalytic residue at L371 (P = 0.1388);
MVP		0.90
MPC		0.84
ClinPred		0.71	D
GERP RS		3.6
Varity_R		0.25
gMVP		0.63

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: chr7-29103703;