NM_031311.5:c.778G>C

Variant names:

• chr7-29071859-C-G
• rs1783777565
• NM_031311.5:c.778G>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.778G>C​(p.Asp260His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: CPVL NM_031311.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.06
• Publications: 0 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, 0.864

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031311.5. 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
	CPVL	NM_031311.5	MANE Select	c.778G>C	p.Asp260His	missense	Exon 9 of 13	NP_112601.3
	CPVL	NM_001371264.1		c.820G>C	p.Asp274His	missense	Exon 12 of 16	NP_001358193.1
	CPVL	NM_001348052.1		c.778G>C	p.Asp260His	missense	Exon 11 of 15	NP_001334981.1	Q9H3G5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPVL	ENST00000265394.10	TSL:1 MANE Select	c.778G>C	p.Asp260His	missense	Exon 9 of 13	ENSP00000265394.5	Q9H3G5
	CPVL	ENST00000396276.7	TSL:1	c.778G>C	p.Asp260His	missense	Exon 9 of 13	ENSP00000379572.3	Q9H3G5
	CPVL	ENST00000409850.5	TSL:2	c.778G>C	p.Asp260His	missense	Exon 13 of 17	ENSP00000387164.1	Q9H3G5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 30

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000756

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	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.075	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	-0.013	T
MutationAssessor	Pathogenic	3.8	H
PhyloP100		7.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Uncertain	0.54
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.83
MutPred		0.67		Loss of ubiquitination at K264 (P = 0.045)
MVP		0.85
MPC		0.90
ClinPred		1.0	D
GERP RS		5.7
PromoterAI		-0.023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.95
gMVP		0.81
Mutation Taster		=27/73	disease causing

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: rs1783777565; hg19: chr7-29111475;