chr3-15458206-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_005677.4(COLQ):c.934A>G(p.Ser312Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0191 in 1,613,888 control chromosomes in the GnomAD database, including 1,008 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 455 hom., cov: 32)

Exomes 𝑓: 0.016 ( 553 hom. )

Consequence

COLQ
NM_005677.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.951

Publications

7 publications found

Variant links:

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]

COLQ Gene-Disease associations (from GenCC):

congenital myasthenic syndrome 5
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia

COLQ links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 16 curated pathogenic missense variants (we use a threshold of 10). The gene has 5 curated benign missense variants. Gene score misZ: -0.21928 (below the threshold of 3.09). Trascript score misZ: -0.17745 (below the threshold of 3.09). GenCC associations: The gene is linked to congenital myasthenic syndrome 5.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016097426).

BP6

Variant 3-15458206-T-C is Benign according to our data. Variant chr3-15458206-T-C is described in ClinVar as Benign. ClinVar VariationId is 128827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
COLQ	NM_005677.4 link	c.934A>G	p.Ser312Gly	missense_variant	Exon 13 of 17	ENST00000383788.10	NP_005668.2
COLQ	NM_080538.2 link	c.904A>G	p.Ser302Gly	missense_variant	Exon 13 of 17		NP_536799.1
COLQ	NM_080539.4 link	c.832A>G	p.Ser278Gly	missense_variant	Exon 12 of 16		NP_536800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COLQ	ENST00000383788.10 link	c.934A>G	p.Ser312Gly	missense_variant	Exon 13 of 17	1	NM_005677.4	ENSP00000373298.3
COLQ	ENST00000603808.5 link	c.934A>G	p.Ser312Gly	missense_variant	Exon 13 of 17	1		ENSP00000474271.1

Frequencies

GnomAD3 genomes

AF:

0.0494

AC:

7523

AN:

152142

Hom.:

454

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0234

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0216

Gnomad FIN

AF:

0.00989

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0132

Gnomad OTH

AF:

0.0454

GnomAD2 exomes

AF:

0.0216

AC:

5425

AN:

251474

AF XY:

0.0202

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.0118

Gnomad ASJ exome

AF:

0.00883

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0109

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.0192

GnomAD4 exome

AF:

0.0160

AC:

23364

AN:

1461628

Hom.:

553

Cov.:

AF XY:

0.0163

AC XY:

11864

AN XY:

727122

show subpopulations

African (AFR)

AF:

0.149

AC:

4977

AN:

33474

American (AMR)

AF:

0.0132

AC:

589

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0113

AC:

295

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.0267

AC:

2305

AN:

86240

European-Finnish (FIN)

AF:

0.0131

AC:

699

AN:

53418

Middle Eastern (MID)

AF:

0.0412

AC:

230

AN:

5586

European-Non Finnish (NFE)

AF:

0.0116

AC:

12901

AN:

1111992

Other (OTH)

AF:

0.0226

AC:

1367

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

1297

2594

3892

5189

6486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

558

1116

1674

2232

2790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0495

AC:

7535

AN:

152260

Hom.:

455

Cov.:

AF XY:

0.0474

AC XY:

3527

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.143

AC:

5919

AN:

41530

American (AMR)

AF:

0.0233

AC:

357

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.0218

AC:

105

AN:

4820

European-Finnish (FIN)

AF:

0.00989

AC:

105

AN:

10612

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0132

AC:

901

AN:

68034

Other (OTH)

AF:

0.0449

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

342

683

1025

1366

1708

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0266

Hom.:

506

Bravo

AF:

0.0549

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.141

AC:

623

ESP6500EA

AF:

0.0138

AC:

119

ExAC

AF:

0.0244

AC:

2960

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0150

EpiControl

AF:

0.0147

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2016

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 04, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Congenital myasthenic syndrome 5

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.20

T;.;.;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.65

T;T;T;T

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.20

N;.;.;.

PhyloP100

0.95

PrimateAI

Benign

0.31

PROVEAN

Benign

0.14

N;N;.;N

REVEL

Benign

0.17

Sift

Benign

0.32

T;T;.;.

Sift4G

Benign

0.60

T;T;T;T

Polyphen

0.0040

B;B;.;B

Vest4

0.081

MPC

0.089

ClinPred

0.0065

GERP RS

2.3

Varity_R

0.031

gMVP

0.25

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over