16-89583743-G-C

Position:

• chr16-89583743-G-C

Variant summary

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

The NM_153636.3(CPNE7):​c.404G>C​(p.Gly135Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CPNE7 NM_153636.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.25

Genes affected

CPNE7 (HGNC:2320): (copine 7) This gene encodes a member of the copine family, which is composed of calcium-dependent membrane-binding proteins. The gene product contains two N-terminal C2 domains and one von Willebrand factor A domain. The encoded protein may be involved in membrane trafficking. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 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	Protein	UniProt
CPNE7	NM_153636.3	c.404G>C	p.Gly135Ala	missense_variant	3/15	ENST00000319518.13	NP_705900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE7	ENST00000319518.13	c.404G>C	p.Gly135Ala	missense_variant	3/15	1	NM_153636.3	ENSP00000317374.8
CPNE7	ENST00000268720.9	c.629G>C	p.Gly210Ala	missense_variant	5/17	1		ENSP00000268720.5
CPNE7	ENST00000525982.5	n.*126G>C		downstream_gene_variant		5		ENSP00000431863.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2024

The c.629G>C (p.G210A) alteration is located in exon 5 (coding exon 5) of the CPNE7 gene. This alteration results from a G to C substitution at nucleotide position 629, causing the glycine (G) at amino acid position 210 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Benign	0.24
Sift	Uncertain	0.021	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		0.97	D;D
Vest4		0.52
MutPred		0.47		Gain of MoRF binding (P = 0.1228);.;
MVP		0.72
MPC		0.38
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.50
gMVP		0.73

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: chr16-89650151;