chr12-38762187-A-T

Variant names:

• chr12-38762187-A-T
• rs1231538454
• NM_153634.3:c.605T>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_153634.3(CPNE8):​c.605T>A​(p.Val202Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. V202I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CPNE8 NM_153634.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.99
• Publications: 0 publications found

Genes affected

CPNE8 (HGNC:23498): (copine 8) Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene is one of several genes that encode a calcium-dependent protein containing two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.836

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153634.3. 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
	CPNE8	NM_153634.3	MANE Select	c.605T>A	p.Val202Asp	missense	Exon 9 of 20	NP_705898.1	Q86YQ8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE8	ENST00000331366.10	TSL:1 MANE Select	c.605T>A	p.Val202Asp	missense	Exon 9 of 20	ENSP00000329748.5	Q86YQ8-1
	CPNE8	ENST00000360449.3	TSL:2	c.569T>A	p.Val190Asp	missense	Exon 9 of 20	ENSP00000353633.3	E7ENV7
	CPNE8	ENST00000862791.1		c.605T>A	p.Val202Asp	missense	Exon 9 of 20	ENSP00000532850.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 33

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	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.073	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.38	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		9.0
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.39	B
Vest4		0.86
MutPred		0.68		Gain of disorder (P = 0.0336)
MVP		0.56
MPC		0.81
ClinPred		1.0	D
GERP RS		3.9
Varity_R		0.94
gMVP		0.86
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

dbSNP: rs1231538454; hg19: chr12-39155989;