7-29066031-G-A

Variant names:

• chr7-29066031-G-A
• rs146316329
• NM_031311.5:c.955C>T

Variant summary

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

The NM_031311.5(CPVL):​c.955C>T​(p.Arg319Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000398 in 1,583,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R319Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: CPVL NM_031311.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.07
• Publications: 2 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 0 ACMG points.

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.955C>T	p.Arg319Trp	missense	Exon 10 of 13	NP_112601.3
	CPVL	NM_001371264.1		c.997C>T	p.Arg333Trp	missense	Exon 13 of 16	NP_001358193.1
	CPVL	NM_001348052.1		c.955C>T	p.Arg319Trp	missense	Exon 12 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.955C>T	p.Arg319Trp	missense	Exon 10 of 13	ENSP00000265394.5	Q9H3G5
	CPVL	ENST00000396276.7	TSL:1	c.955C>T	p.Arg319Trp	missense	Exon 10 of 13	ENSP00000379572.3	Q9H3G5
	CPVL	ENST00000409850.5	TSL:2	c.955C>T	p.Arg319Trp	missense	Exon 14 of 17	ENSP00000387164.1	Q9H3G5

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 151996 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.0000294

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.0000928 AC: 22 AN: 236992 AF XY: 0.0000704

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000656

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000910

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000377 AC: 54 AN: 1431006 Hom.: 0 Cov.: 27 AF XY: 0.0000323 AC XY: 23 AN XY: 712278

African (AFR) AF: 0.00 AC: 0 AN: 32346

American (AMR) AF: 0.000537 AC: 22 AN: 40954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25346

East Asian (EAS) AF: 0.00 AC: 0 AN: 39332

South Asian (SAS) AF: 0.0000244 AC: 2 AN: 81972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5668

European-Non Finnish (NFE) AF: 0.0000265 AC: 29 AN: 1092934

Other (OTH) AF: 0.0000169 AC: 1 AN: 59290

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152114 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74358

African (AFR) AF: 0.0000241 AC: 1 AN: 41500

American (AMR) AF: 0.000262 AC: 4 AN: 15272

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67992

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.0000941 Hom.: 0

Bravo AF: 0.0000982

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000576 AC: 7

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	Benign	0.093
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	0.23	D
MutationAssessor	Benign	1.6	L
PhyloP100		3.1
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.44
Sift	Benign	0.24	T
Sift4G	Benign	0.20	T
Polyphen		1.0	D
Vest4		0.34
MVP		0.97
MPC		0.63
ClinPred		0.25	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.20
gMVP		0.52
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.22		Position offset: -8

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs146316329; hg19: chr7-29105647; COSMIC: COSV107204459; COSMIC: COSV107204459;