chr7-29030704-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_031311.5(CPVL):​c.1193G>T​(p.Arg398Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,110 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.815

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPVL	NM_031311.5	MANE Select	c.1193G>T	p.Arg398Leu	missense	Exon 12 of 13	NP_112601.3
	CPVL	NM_001371264.1		c.1235G>T	p.Arg412Leu	missense	Exon 15 of 16	NP_001358193.1
	CPVL	NM_001348052.1		c.1193G>T	p.Arg398Leu	missense	Exon 14 of 15	NP_001334981.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPVL	ENST00000265394.10	TSL:1 MANE Select	c.1193G>T	p.Arg398Leu	missense	Exon 12 of 13	ENSP00000265394.5
	CPVL	ENST00000396276.7	TSL:1	c.1193G>T	p.Arg398Leu	missense	Exon 12 of 13	ENSP00000379572.3
	CPVL	ENST00000409850.5	TSL:2	c.1193G>T	p.Arg398Leu	missense	Exon 16 of 17	ENSP00000387164.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151918 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461192 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 726862

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111700

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151918 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74182

African (AFR) AF: 0.00 AC: 0 AN: 41332

American (AMR) AF: 0.00 AC: 0 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 8758

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.074
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.053	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		1.1
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.23
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.022	D
Polyphen		0.97	D
Vest4		0.40
MutPred		0.64		Loss of MoRF binding (P = 0.0922)
MVP		0.49
MPC		0.35
ClinPred		0.98	D
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.70
gMVP		0.71
Mutation Taster		=71/29	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;