6-36745446-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_020939.2(CPNE5):c.1270C>T(p.Arg424Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000985 in 1,604,354 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00010 ( 0 hom. )
Consequence
CPNE5
NM_020939.2 missense
NM_020939.2 missense
Scores
4
8
7
Clinical Significance
Conservation
PhyloP100: 3.82
Genes affected
CPNE5 (HGNC:2318): (copine 5) 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. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. More variants may exist, but their full-length natures could not be determined. [provided by RefSeq, Sep 2015]
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ACMG classification
Classification made for transcript
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 |
---|---|---|---|---|---|---|---|---|
CPNE5 | NM_020939.2 | c.1270C>T | p.Arg424Cys | missense_variant | 17/21 | ENST00000244751.7 | NP_065990.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CPNE5 | ENST00000244751.7 | c.1270C>T | p.Arg424Cys | missense_variant | 17/21 | 1 | NM_020939.2 | ENSP00000244751.2 |
Frequencies
GnomAD3 genomes AF: 0.0000788 AC: 12AN: 152258Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000656 AC: 15AN: 228540Hom.: 0 AF XY: 0.0000567 AC XY: 7AN XY: 123400
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GnomAD4 exome AF: 0.000101 AC: 146AN: 1451978Hom.: 0 Cov.: 31 AF XY: 0.0000971 AC XY: 70AN XY: 721188
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GnomAD4 genome AF: 0.0000788 AC: 12AN: 152376Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74510
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 17, 2023 | The c.1270C>T (p.R424C) alteration is located in exon 17 (coding exon 17) of the CPNE5 gene. This alteration results from a C to T substitution at nucleotide position 1270, causing the arginine (R) at amino acid position 424 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
.;T
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Benign
T;D
Polyphen
1.0
.;D
Vest4
MVP
MPC
1.7
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at