Variant rs116373583 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_005677.4(COLQ):c.1108G>T(p.Asp370Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

COLQ
NM_005677.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.17

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 links:

COLQ (HGNC:):

COLQ links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.76

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COLQ	NM_005677.4 linkuse as main transcript	c.1108G>T	p.Asp370Tyr	missense_variant	15/17	ENST00000383788.10	NP_005668.2	Q9Y215-1
COLQ	NM_080538.2 linkuse as main transcript	c.1078G>T	p.Asp360Tyr	missense_variant	15/17		NP_536799.1	Q9Y215-2
COLQ	NM_080539.4 linkuse as main transcript	c.1006G>T	p.Asp336Tyr	missense_variant	14/16		NP_536800.2	Q9Y215-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COLQ	ENST00000383788.10 linkuse as main transcript	c.1108G>T	p.Asp370Tyr	missense_variant	15/17	1	NM_005677.4	ENSP00000373298.3	Q9Y215-1
COLQ	ENST00000603808.5 linkuse as main transcript	c.1108G>T	p.Asp370Tyr	missense_variant	15/17	1		ENSP00000474271.1	A0A0C4DGS2
EAF1-AS1	ENST00000629729.2 linkuse as main transcript	n.-46G>T		upstream_gene_variant		5		ENSP00000518887.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251238

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.70

D;.;.;.

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Pathogenic

0.33

MetaRNN

Pathogenic

0.76

D;D;D;D

MetaSVM

Uncertain

0.79

MutationAssessor

Uncertain

2.1

M;.;.;.

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.5

D;D;.;D

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0010

D;D;.;.

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

0.99

D;D;.;D

Vest4

0.59

MutPred

0.49

Gain of solvent accessibility (P = 0.0133);.;Gain of solvent accessibility (P = 0.0133);.;

MVP

0.96

MPC

0.12

ClinPred

0.89

GERP RS

5.0

Varity_R

0.46

gMVP

0.69

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over