3-15451279-T-A

Variant names:

• chr3-15451279-T-A
• rs2278962
• NM_005677.4:c.*365A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005677.4(COLQ):​c.*365A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 356,538 control chromosomes in the GnomAD database, including 33,768 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (14842 hom., cov: 31)
  • Exomes 𝑓: 0.43 (18926 hom.)
• Consequence: COLQ NM_005677.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.550
• Publications: 7 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 3-15451279-T-A is Benign according to our data. Variant chr3-15451279-T-A is described in ClinVar as Benign. ClinVar VariationId is 343839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

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.*365A>T		3_prime_UTR	Exon 17 of 17	NP_005668.2
	COLQ	NM_080538.2		c.*365A>T		3_prime_UTR	Exon 17 of 17	NP_536799.1	Q9Y215-2
	COLQ	NM_080539.4		c.*365A>T		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.*365A>T		3_prime_UTR	Exon 17 of 17	ENSP00000373298.3	Q9Y215-1
	ENSG00000293553	ENST00000629729.3	TSL:5	n.*291+166A>T		intron	N/A	ENSP00000518887.1	A0AAA9YHP9
	COLQ	ENST00000874202.1		c.*365A>T		3_prime_UTR	Exon 17 of 17	ENSP00000544261.1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67110 AN: 151710 Hom.: 14816 Cov.: 31

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.476

GnomAD4 exome AF: 0.425 AC: 87069 AN: 204710 Hom.: 18926 Cov.: 0 AF XY: 0.425 AC XY: 46417 AN XY: 109282

African (AFR) AF: 0.494 AC: 3162 AN: 6404

American (AMR) AF: 0.383 AC: 4274 AN: 11162

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 2631 AN: 5418

East Asian (EAS) AF: 0.486 AC: 5135 AN: 10560

South Asian (SAS) AF: 0.424 AC: 13603 AN: 32096

European-Finnish (FIN) AF: 0.341 AC: 3539 AN: 10368

Middle Eastern (MID) AF: 0.487 AC: 375 AN: 770

European-Non Finnish (NFE) AF: 0.423 AC: 49531 AN: 117028

Other (OTH) AF: 0.442 AC: 4819 AN: 10904

GnomAD4 genome AF: 0.443 AC: 67186 AN: 151828 Hom.: 14842 Cov.: 31 AF XY: 0.439 AC XY: 32591 AN XY: 74206

African (AFR) AF: 0.491 AC: 20343 AN: 41396

American (AMR) AF: 0.421 AC: 6437 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1686 AN: 3472

East Asian (EAS) AF: 0.491 AC: 2539 AN: 5166

South Asian (SAS) AF: 0.411 AC: 1975 AN: 4802

European-Finnish (FIN) AF: 0.349 AC: 3664 AN: 10508

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28908 AN: 67896

Other (OTH) AF: 0.482 AC: 1016 AN: 2110

Alfa AF: 0.426 Hom.: 1746

Bravo AF: 0.451

Asia WGS AF: 0.420 AC: 1457 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

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	-0.94
CADD	Benign	1.5
DANN	Benign	0.44
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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: rs2278962; hg19: chr3-15492786; COSMIC: COSV67524966; COSMIC: COSV67524966;