rs144627537

Variant names:

• chr10-100057048-C-G
• NM_001308.3:c.976G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-100057048-C-G
• chr10-100057048-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001308.3(CPN1):​c.976G>C​(p.Gly326Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPN1 NM_001308.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.40

Genes affected

CPN1 (HGNC:2312): (carboxypeptidase N subunit 1) Carboxypeptidase N is a plasma metallo-protease that cleaves basic amino acids from the C terminal of peptides and proteins. The enzyme is important in the regulation of peptides like kinins and anaphylatoxins, and has also been known as kininase-1 and anaphylatoxin inactivator. This enzyme is a tetramer comprised of two identical regulatory subunits and two identical catalytic subunits; this gene encodes the catalytic subunit. Mutations in this gene can be associated with angioedema or chronic urticaria resulting from carboxypeptidase N deficiency. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33075064).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPN1	NM_001308.3	c.976G>C	p.Gly326Arg	missense_variant	Exon 6 of 9	ENST00000370418.8	NP_001299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPN1	ENST00000370418.8	c.976G>C	p.Gly326Arg	missense_variant	Exon 6 of 9	1	NM_001308.3	ENSP00000359446.3
CPN1	ENST00000441382.1	c.367G>C	p.Gly123Arg	missense_variant	Exon 3 of 5	2		ENSP00000410895.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.56	N;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.085
Sift	Benign	0.077	T;T
Sift4G	Benign	0.29	T;T
Polyphen		1.0	D;.
Vest4		0.45
MutPred		0.40		Gain of solvent accessibility (P = 0.0674);.;
MVP		0.41
MPC		1.3
ClinPred		0.93	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.55
gMVP		0.77

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: chr10-101816805;