chr20-35631982-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_152925.3(CPNE1):āc.500A>Gā(p.Gln167Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,613,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 32)
Exomes š: 0.000031 ( 0 hom. )
Consequence
CPNE1
NM_152925.3 missense
NM_152925.3 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 3.98
Genes affected
CPNE1 (HGNC:2314): (copine 1) Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene encodes a calcium-dependent protein that also contains two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. However, the encoded protein does not contain a predicted signal sequence or transmembrane domains. This protein has a broad tissue distribution and it may function in membrane trafficking. This gene and the gene for RNA binding motif protein 12 overlap at map location 20q11.21. Alternate splicing results in multiple transcript variants encoding different proteins. [provided by RefSeq, Aug 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1966277).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPNE1 | NM_152925.3 | c.500A>G | p.Gln167Arg | missense_variant | 6/16 | ENST00000397443.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPNE1 | ENST00000397443.7 | c.500A>G | p.Gln167Arg | missense_variant | 6/16 | 5 | NM_152925.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 151978Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251332Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135848
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GnomAD4 exome AF: 0.0000315 AC: 46AN: 1461620Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18AN XY: 727096
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 151978Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74254
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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 | Oct 02, 2023 | The c.515A>G (p.Q172R) alteration is located in exon 6 (coding exon 6) of the CPNE1 gene. This alteration results from a A to G substitution at nucleotide position 515, causing the glutamine (Q) at amino acid position 172 to be replaced by an arginine (R). 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
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.;.;T;T;T;T;T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
.;T;T;T;T;T;T;T;T;T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;.;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;.;.;.;.;.;.;T;.;T
Polyphen
B;B;B;P;.;.;.;.;.;.;.;.;.
Vest4
MutPred
0.30
.;Gain of MoRF binding (P = 0.0386);.;.;.;.;.;.;.;.;.;.;.;
MVP
MPC
0.54
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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