Genetic Variant COLQ:p.Ser169* (chr3-15475447-G-T) – ACMG Classification: Pathogenic (10 pts)

Variant summary

Our verdict is . The variant received 10 ACMG points: 10P and 0B. PVS1PM2

The NM_005677.4(COLQ):c.506C>A(p.Ser169*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

COLQ
NM_005677.4 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.22

Publications

0 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

COLQ links:

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new If you want to explore the variant's impact on the transcript NM_005677.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 10 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005677.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COLQ	NM_005677.4	MANE Select	c.506C>A	p.Ser169*	stop_gained	Exon 7 of 17	NP_005668.2
COLQ	NM_080538.2		c.476C>A	p.Ser159*	stop_gained	Exon 7 of 17	NP_536799.1	Q9Y215-2
COLQ	NM_080539.4		c.404C>A	p.Ser135*	stop_gained	Exon 6 of 16	NP_536800.2	Q9Y215-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COLQ	ENST00000383788.10	TSL:1 MANE Select	c.506C>A	p.Ser169*	stop_gained	Exon 7 of 17	ENSP00000373298.3	Q9Y215-1
COLQ	ENST00000603808.5	TSL:1	c.506C>A	p.Ser169*	stop_gained	Exon 7 of 17	ENSP00000474271.1	A0A0C4DGS2
COLQ	ENST00000874202.1		c.506C>A	p.Ser169*	stop_gained	Exon 7 of 17	ENSP00000544261.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1449678

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719692

African (AFR)

AF:

0.00

AC:

AN:

33332

American (AMR)

AF:

0.00

AC:

AN:

43398

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25686

East Asian (EAS)

AF:

0.00

AC:

AN:

39516

South Asian (SAS)

AF:

0.00

AC:

AN:

83950

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52666

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105532

Other (OTH)

AF:

0.00

AC:

AN:

59912

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Pathogenic

0.60

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Uncertain

0.92

PhyloP100

4.2

Mutation Taster

=0/200

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over