rs372064982
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005677.4(COLQ):āc.1072C>Gā(p.Gln358Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Genomes: š 0.000046 ( 0 hom., cov: 32)
Exomes š: 0.000035 ( 0 hom. )
Consequence
COLQ
NM_005677.4 missense, splice_region
NM_005677.4 missense, splice_region
Scores
2
12
5
Splicing: ADA: 0.9298
2
Clinical Significance
Conservation
PhyloP100: 9.72
Genes affected
COLQ (HGNC:2226): (collagen like tail subunit of asymmetric acetylcholinesterase) This gene encodes the subunit of a collagen-like molecule associated with acetylcholinesterase in skeletal muscle. Each molecule is composed of three identical subunits. Each subunit contains a proline-rich attachment domain (PRAD) that binds an acetylcholinesterase tetramer to anchor the catalytic subunit of the enzyme to the basal lamina. Mutations in this gene are associated with endplate acetylcholinesterase deficiency. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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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 | UniProt |
---|---|---|---|---|---|---|---|
COLQ | NM_005677.4 | c.1072C>G | p.Gln358Glu | missense_variant, splice_region_variant | 14/17 | ENST00000383788.10 | |
COLQ | NM_080538.2 | c.1042C>G | p.Gln348Glu | missense_variant, splice_region_variant | 14/17 | ||
COLQ | NM_080539.4 | c.970C>G | p.Gln324Glu | missense_variant, splice_region_variant | 13/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COLQ | ENST00000383788.10 | c.1072C>G | p.Gln358Glu | missense_variant, splice_region_variant | 14/17 | 1 | NM_005677.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152198Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251372Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135866
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GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461776Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24AN XY: 727192
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152316Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74488
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Congenital myasthenic syndrome 5 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 14, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 358 of the COLQ protein (p.Gln358Glu). This variant is present in population databases (rs372064982, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with COLQ-related conditions. ClinVar contains an entry for this variant (Variation ID: 468339). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;.;N
REVEL
Pathogenic
Sift
Uncertain
D;D;.;.
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;.;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at