3-194341790-C-T

Position:

• chr3-194341790-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080513.4(CPN2):​c.913G>A​(p.Ala305Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,613,682 control chromosomes in the GnomAD database, including 74,095 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.33 (8607 hom., cov: 32)
  • Exomes 𝑓: 0.30 (65488 hom.)
• Consequence: CPN2 NM_001080513.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.784

Genes affected

CPN2 (HGNC:2313): (carboxypeptidase N subunit 2) Predicted to be involved in regulation of catalytic activity. Located in blood microparticle and extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.7690015E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPN2	NM_001080513.4	c.913G>A	p.Ala305Thr	missense_variant	2/2	ENST00000323830.4	NP_001073982.3
CPN2	NM_001291988.2	c.913G>A	p.Ala305Thr	missense_variant	2/2		NP_001278917.1
CPN2	XM_005269280.5	c.913G>A	p.Ala305Thr	missense_variant	3/3		XP_005269337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPN2	ENST00000323830.4	c.913G>A	p.Ala305Thr	missense_variant	2/2	1	NM_001080513.4	ENSP00000319464	P1
CPN2	ENST00000429275.1	c.913G>A	p.Ala305Thr	missense_variant	2/2	5		ENSP00000402232	P1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50173 AN: 151830 Hom.: 8603 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.304

GnomAD3 exomes AF: 0.310 AC: 77937 AN: 251038 Hom.: 12896 AF XY: 0.314 AC XY: 42602 AN XY: 135704

Gnomad AFR exome AF: 0.431

Gnomad AMR exome AF: 0.218

Gnomad ASJ exome AF: 0.345

Gnomad EAS exome AF: 0.339

Gnomad SAS exome AF: 0.405

Gnomad FIN exome AF: 0.355

Gnomad NFE exome AF: 0.280

Gnomad OTH exome AF: 0.304

GnomAD4 exome AF: 0.295 AC: 431658 AN: 1461734 Hom.: 65488 Cov.: 81 AF XY: 0.298 AC XY: 216801 AN XY: 727154

Gnomad4 AFR exome AF: 0.429

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.356

Gnomad4 SAS exome AF: 0.407

Gnomad4 FIN exome AF: 0.355

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.304

GnomAD4 genome AF: 0.330 AC: 50206 AN: 151948 Hom.: 8607 Cov.: 32 AF XY: 0.334 AC XY: 24796 AN XY: 74258

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.306

Alfa AF: 0.294 Hom.: 15794

Bravo AF: 0.325

TwinsUK AF: 0.286 AC: 1061

ALSPAC AF: 0.288 AC: 1111

ESP6500AA AF: 0.410 AC: 1807

ESP6500EA AF: 0.283 AC: 2431

ExAC AF: 0.314 AC: 38128

Asia WGS AF: 0.384 AC: 1334 AN: 3478

EpiCase AF: 0.285

EpiControl AF: 0.278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.37
DANN	Benign	0.60
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.40	.;T
MetaRNN	Benign	0.00068	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.38	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.22	N;N
REVEL	Benign	0.11
Sift	Benign	0.30	T;T
Sift4G	Benign	0.44	T;T
Polyphen		0.017	B;B
Vest4		0.0090
MPC		0.18
ClinPred		0.0095	T
GERP RS		-11
Varity_R		0.052
gMVP		0.30

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

LitVar

Other links and lift over

dbSNP: rs3732477; hg19: chr3-194062519;