rs11711157

Variant names:

• chr3-194341097-C-G
• NM_001080513.4:c.1606G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-194341097-C-G
• chr3-194341097-C-T

Variant summary

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

The NM_001080513.4(CPN2):​c.1606G>C​(p.Val536Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V536M) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CPN2 NM_001080513.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.528

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 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=0.11704481).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPN2	NM_001080513.4	c.1606G>C	p.Val536Leu	missense_variant	Exon 2 of 2	ENST00000323830.4	NP_001073982.3
CPN2	NM_001291988.2	c.1606G>C	p.Val536Leu	missense_variant	Exon 2 of 2		NP_001278917.1
CPN2	XM_005269280.5	c.1606G>C	p.Val536Leu	missense_variant	Exon 3 of 3		XP_005269337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPN2	ENST00000323830.4	c.1606G>C	p.Val536Leu	missense_variant	Exon 2 of 2	1	NM_001080513.4	ENSP00000319464.3
CPN2	ENST00000429275.1	c.1606G>C	p.Val536Leu	missense_variant	Exon 2 of 2	5		ENSP00000402232.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455764 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 723138

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.49	.;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.27	N;N
REVEL	Benign	0.041
Sift	Uncertain	0.018	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.031	B;B
Vest4		0.077
MutPred		0.40		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP		0.56
MPC		0.23
ClinPred		0.13	T
GERP RS		2.8
Varity_R		0.056
gMVP		0.15

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: chr3-194061826;