NM_005677.4:c.*516G>A

Variant names:

• chr3-15451128-C-T
• rs544927968
• NM_005677.4:c.*516G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_005677.4(COLQ):​c.*516G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00063 in 165,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00062 (0 hom.)
• Consequence: COLQ NM_005677.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.37
• Publications: 0 publications found

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)

ENSG00000293553 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000631 (96/152196) while in subpopulation SAS AF = 0.0025 (12/4802). AF 95% confidence interval is 0.00144. There are 0 homozygotes in GnomAd4. There are 58 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLQ	NM_005677.4	MANE Select	c.*516G>A		3_prime_UTR	Exon 17 of 17	NP_005668.2
	COLQ	NM_080538.2		c.*516G>A		3_prime_UTR	Exon 17 of 17	NP_536799.1	Q9Y215-2
	COLQ	NM_080539.4		c.*516G>A		3_prime_UTR	Exon 16 of 16	NP_536800.2	Q9Y215-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLQ	ENST00000383788.10	TSL:1 MANE Select	c.*516G>A		3_prime_UTR	Exon 17 of 17	ENSP00000373298.3	Q9Y215-1
	ENSG00000293553	ENST00000629729.3	TSL:5	n.*291+317G>A		intron	N/A	ENSP00000518887.1	A0AAA9YHP9
	COLQ	ENST00000874202.1		c.*516G>A		3_prime_UTR	Exon 17 of 17	ENSP00000544261.1

Frequencies

GnomAD3 genomes AF: 0.000631 AC: 96 AN: 152078 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00250

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000624 AC: 8 AN: 12828 Hom.: 0 Cov.: 0 AF XY: 0.000866 AC XY: 6 AN XY: 6930

African (AFR) AF: 0.00 AC: 0 AN: 390

American (AMR) AF: 0.00326 AC: 7 AN: 2146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 182

East Asian (EAS) AF: 0.00 AC: 0 AN: 886

South Asian (SAS) AF: 0.000790 AC: 1 AN: 1266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 40

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6862

Other (OTH) AF: 0.00 AC: 0 AN: 548

GnomAD4 genome AF: 0.000631 AC: 96 AN: 152196 Hom.: 0 Cov.: 32 AF XY: 0.000780 AC XY: 58 AN XY: 74400

African (AFR) AF: 0.000866 AC: 36 AN: 41556

American (AMR) AF: 0.00150 AC: 23 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00250 AC: 12 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000567

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Congenital myasthenic syndrome 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.64
PhyloP100		-2.4
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs544927968; hg19: chr3-15492635;