3-15478979-T-A

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_005677.4(COLQ):​c.391A>T​(p.Lys131*) variant causes a stop gained, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. 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)

Consequence

COLQ
NM_005677.4 stop_gained, splice_region

Scores

4
2
1
Splicing: ADA: 0.9684
1
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.72
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]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 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;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COLQNM_005677.4 linkuse as main transcriptc.391A>T p.Lys131* stop_gained, splice_region_variant 5/17 ENST00000383788.10 NP_005668.2 Q9Y215-1
COLQNM_080538.2 linkuse as main transcriptc.361A>T p.Lys121* stop_gained, splice_region_variant 5/17 NP_536799.1 Q9Y215-2
COLQNM_080539.4 linkuse as main transcriptc.289A>T p.Lys97* stop_gained, splice_region_variant 4/16 NP_536800.2 Q9Y215-3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COLQENST00000383788.10 linkuse as main transcriptc.391A>T p.Lys131* stop_gained, splice_region_variant 5/171 NM_005677.4 ENSP00000373298.3 Q9Y215-1
COLQENST00000603808.5 linkuse as main transcriptc.391A>T p.Lys131* stop_gained, splice_region_variant 5/171 ENSP00000474271.1 A0A0C4DGS2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.62
CADD
Pathogenic
63
DANN
Uncertain
1.0
Eigen
Pathogenic
0.79
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Pathogenic
0.97
D
Vest4
0.86
GERP RS
5.3

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
0.97
dbscSNV1_RF
Benign
0.69
SpliceAI score (max)
0.61
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.58
Position offset: 2
DS_DL_spliceai
0.61
Position offset: -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.

Other links and lift over

dbSNP: rs142980906; hg19: chr3-15520486; API