8-86528553-C-T

Position:

• chr8-86528553-C-T

Variant summary

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

The NM_003909.5(CPNE3):​c.8C>T​(p.Ala3Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,350 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: CPNE3 NM_003909.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

Genes affected

CPNE3 (HGNC:2316): (copine 3) Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene encodes a protein which contains two type II C2 domains in the amino-terminus and an A domain-like sequence in the carboxy-terminus. The A domain mediates interactions between integrins and extracellular ligands. [provided by RefSeq, Aug 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPNE3	NM_003909.5	c.8C>T	p.Ala3Val	missense_variant	3/17	ENST00000517490.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPNE3	ENST00000517490.6	c.8C>T	p.Ala3Val	missense_variant	3/17	1	NM_003909.5	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 250636 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135492

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000875

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461350 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 726970

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000157

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: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	T;T;T;.;T;.;T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D;.;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.48	T;T;T;T;T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.5	M;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.66	T
Sift4G	Uncertain	0.0080	D;D;D;.;D;D;D
Polyphen		0.98	D;.;.;.;.;.;.
Vest4		0.52
MutPred		0.36		Loss of disorder (P = 0.0687);Loss of disorder (P = 0.0687);Loss of disorder (P = 0.0687);Loss of disorder (P = 0.0687);Loss of disorder (P = 0.0687);Loss of disorder (P = 0.0687);Loss of disorder (P = 0.0687);
MVP		0.70
ClinPred		0.93	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs967728616; hg19: chr8-87540781;