7-29071863-C-G

Position:

• chr7-29071863-C-G

Variant summary

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

The NM_031311.5(CPVL):​c.774G>C​(p.Leu258Phe) 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: 30)
• Consequence: CPVL NM_031311.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.83

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPVL	NM_031311.5	c.774G>C	p.Leu258Phe	missense_variant	9/13	ENST00000265394.10	NP_112601.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPVL	ENST00000265394.10	c.774G>C	p.Leu258Phe	missense_variant	9/13	1	NM_031311.5	ENSP00000265394.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 30

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 10, 2024

The c.774G>C (p.L258F) alteration is located in exon 9 (coding exon 8) of the CPVL gene. This alteration results from a G to C substitution at nucleotide position 774, causing the leucine (L) at amino acid position 258 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	Benign	0.22
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D;D;.;D;.
Eigen	Uncertain	0.33
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	.;.;T;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.83	D;D;D;D;D
MetaSVM	Uncertain	0.47	D
MutationAssessor	Uncertain	2.6	M;M;.;M;.
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.3	D;D;N;D;D
REVEL	Uncertain	0.60
Sift	Benign	0.053	T;T;D;T;T
Sift4G	Uncertain	0.033	D;D;D;D;.
Polyphen		0.98	D;D;.;D;.
Vest4		0.28
MutPred		0.74		Gain of methylation at K262 (P = 0.0669);Gain of methylation at K262 (P = 0.0669);.;Gain of methylation at K262 (P = 0.0669);.;
MVP		0.96
MPC		0.80
ClinPred		0.97	D
GERP RS		0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr7-29111479;