rs533015053

Variant names:

• chr3-15451223-C-T
• rs533015053
• NM_005677.4:c.*421G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005677.4(COLQ):​c.*421G>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 0.000296 in 263,956 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 0.00045 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000089 (0 hom.)
• Consequence: COLQ NM_005677.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -2.27
• 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia

ENSG00000293553 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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.*421G>A		3_prime_UTR	Exon 17 of 17	NP_005668.2
	COLQ	NM_080538.2		c.*421G>A		3_prime_UTR	Exon 17 of 17	NP_536799.1	Q9Y215-2
	COLQ	NM_080539.4		c.*421G>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.*421G>A		3_prime_UTR	Exon 17 of 17	ENSP00000373298.3	Q9Y215-1
	ENSG00000293553	ENST00000629729.3	TSL:5	n.*291+222G>A		intron	N/A	ENSP00000518887.1	A0AAA9YHP9
	COLQ	ENST00000874202.1		c.*421G>A		3_prime_UTR	Exon 17 of 17	ENSP00000544261.1

Frequencies

GnomAD3 genomes AF: 0.000447 AC: 68 AN: 152044 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.0000895 AC: 10 AN: 111794 Hom.: 0 Cov.: 0 AF XY: 0.0000510 AC XY: 3 AN XY: 58878

African (AFR) AF: 0.000926 AC: 4 AN: 4320

American (AMR) AF: 0.000457 AC: 3 AN: 6562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2820

East Asian (EAS) AF: 0.00 AC: 0 AN: 6434

South Asian (SAS) AF: 0.0000641 AC: 1 AN: 15604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5050

Middle Eastern (MID) AF: 0.00236 AC: 1 AN: 424

European-Non Finnish (NFE) AF: 0.0000154 AC: 1 AN: 64754

Other (OTH) AF: 0.00 AC: 0 AN: 5826

GnomAD4 genome AF: 0.000447 AC: 68 AN: 152162 Hom.: 0 Cov.: 31 AF XY: 0.000511 AC XY: 38 AN XY: 74400

African (AFR) AF: 0.00116 AC: 48 AN: 41530

American (AMR) AF: 0.000720 AC: 11 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67982

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.000277 Hom.: 0

Bravo AF: 0.000457

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Congenital myasthenic syndrome 5 (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.27
DANN	Benign	0.62
PhyloP100		-2.3

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: rs533015053; hg19: chr3-15492730;