7-29064111-T-C

Position:

• chr7-29064111-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031311.5(CPVL):​c.1087A>G​(p.Thr363Ala) 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. 16/21 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: CPVL NM_031311.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2117098).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPVL	NM_031311.5	c.1087A>G	p.Thr363Ala	missense_variant	11/13	ENST00000265394.10	NP_112601.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPVL	ENST00000265394.10	c.1087A>G	p.Thr363Ala	missense_variant	11/13	1	NM_031311.5	ENSP00000265394	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Aug 02, 2023

The c.1087A>G (p.T363A) alteration is located in exon 11 (coding exon 10) of the CPVL gene. This alteration results from a A to G substitution at nucleotide position 1087, causing the threonine (T) at amino acid position 363 to be replaced by an alanine (A). 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	0.13
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	15
DANN	Benign	0.80
DEOGEN2	Benign	0.23	T;T;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.52	.;.;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L;L;L
MutationTaster	Benign	0.78	N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.22
Sift	Benign	0.073	T;T;T
Sift4G	Benign	0.069	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.28
MutPred		0.52		Loss of phosphorylation at T363 (P = 0.0651);Loss of phosphorylation at T363 (P = 0.0651);Loss of phosphorylation at T363 (P = 0.0651);
MVP		0.87
MPC		0.23
ClinPred		0.16	T
GERP RS		0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.076
gMVP		0.42

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: chr7-29103727;