4-786635-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_006651.4(CPLX1):c.271G>A(p.Glu91Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,612,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
CPLX1
NM_006651.4 missense
NM_006651.4 missense
Scores
2
11
6
Clinical Significance
Conservation
PhyloP100: 3.74
Genes affected
CPLX1 (HGNC:2309): (complexin 1) Proteins encoded by the complexin/synaphin gene family are cytosolic proteins that function in synaptic vesicle exocytosis. These proteins bind syntaxin, part of the SNAP receptor. The protein product of this gene binds to the SNAP receptor complex and disrupts it, allowing transmitter release. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38149673).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPLX1 | NM_006651.4 | c.271G>A | p.Glu91Lys | missense_variant | 4/4 | ENST00000304062.11 | |
CPLX1 | XM_011513391.2 | c.226G>A | p.Glu76Lys | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPLX1 | ENST00000304062.11 | c.271G>A | p.Glu91Lys | missense_variant | 4/4 | 1 | NM_006651.4 | P1 | |
CPLX1 | ENST00000505203.1 | c.208G>A | p.Glu70Lys | missense_variant | 5/5 | 2 | |||
CPLX1 | ENST00000504062.1 | c.226G>A | p.Glu76Lys | missense_variant | 3/3 | 3 | |||
CPLX1 | ENST00000506404.1 | n.324G>A | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151966Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
2
AN:
151966
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000243 AC: 6AN: 246894Hom.: 0 AF XY: 0.0000446 AC XY: 6AN XY: 134476
GnomAD3 exomes
AF:
AC:
6
AN:
246894
Hom.:
AF XY:
AC XY:
6
AN XY:
134476
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1460386Hom.: 0 Cov.: 36 AF XY: 0.0000179 AC XY: 13AN XY: 726538
GnomAD4 exome
AF:
AC:
22
AN:
1460386
Hom.:
Cov.:
36
AF XY:
AC XY:
13
AN XY:
726538
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151966Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74230
GnomAD4 genome
AF:
AC:
2
AN:
151966
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74230
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2021 | The c.271G>A (p.E91K) alteration is located in exon 4 (coding exon 3) of the CPLX1 gene. This alteration results from a G to A substitution at nucleotide position 271, causing the glutamic acid (E) at amino acid position 91 to be replaced by a lysine (K). 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
D
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;D;N
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;T
Polyphen
D;D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at