3-15453879-G-A

Variant names:

• chr3-15453879-G-A
• rs55866379
• NM_005677.4:c.1248C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_005677.4(COLQ):​c.1248C>T​(p.Asp416Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 1,612,056 control chromosomes in the GnomAD database, including 870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (62 hom., cov: 32)
  • Exomes 𝑓: 0.031 (808 hom.)
• Consequence: COLQ NM_005677.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 2.50
• Publications: 6 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 3-15453879-G-A is Benign according to our data. Variant chr3-15453879-G-A is described in ClinVar as Benign. ClinVar VariationId is 128825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.5 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0238 (3619/152214) while in subpopulation NFE AF = 0.0346 (2351/68016). AF 95% confidence interval is 0.0334. There are 62 homozygotes in GnomAd4. There are 1737 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 62 AR gene

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.1248C>T	p.Asp416Asp	synonymous	Exon 16 of 17	NP_005668.2
	COLQ	NM_080538.2		c.1218C>T	p.Asp406Asp	synonymous	Exon 16 of 17	NP_536799.1	Q9Y215-2
	COLQ	NM_080539.4		c.1146C>T	p.Asp382Asp	synonymous	Exon 15 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.1248C>T	p.Asp416Asp	synonymous	Exon 16 of 17	ENSP00000373298.3	Q9Y215-1
	COLQ	ENST00000603808.5	TSL:1	c.1251C>T	p.Asp417Asp	synonymous	Exon 16 of 17	ENSP00000474271.1	A0A0C4DGS2
	ENSG00000293553	ENST00000629729.3	TSL:5	n.95C>T		non_coding_transcript_exon	Exon 2 of 6	ENSP00000518887.1	A0AAA9YHP9

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3619 AN: 152096 Hom.: 62 Cov.: 32

Gnomad AFR AF: 0.00877

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0233

Gnomad FIN AF: 0.0125

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0346

Gnomad OTH AF: 0.0345

GnomAD2 exomes AF: 0.0241 AC: 5975 AN: 247810 AF XY: 0.0261

Gnomad AFR exome AF: 0.00842

Gnomad AMR exome AF: 0.0181

Gnomad ASJ exome AF: 0.0139

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.0141

Gnomad NFE exome AF: 0.0330

Gnomad OTH exome AF: 0.0319

GnomAD4 exome AF: 0.0313 AC: 45629 AN: 1459842 Hom.: 808 Cov.: 32 AF XY: 0.0317 AC XY: 23046 AN XY: 726034

African (AFR) AF: 0.00733 AC: 245 AN: 33438

American (AMR) AF: 0.0192 AC: 858 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.0165 AC: 431 AN: 26100

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39608

South Asian (SAS) AF: 0.0314 AC: 2692 AN: 85778

European-Finnish (FIN) AF: 0.0169 AC: 901 AN: 53294

Middle Eastern (MID) AF: 0.0517 AC: 298 AN: 5762

European-Non Finnish (NFE) AF: 0.0345 AC: 38282 AN: 1110946

Other (OTH) AF: 0.0318 AC: 1919 AN: 60316

GnomAD4 genome AF: 0.0238 AC: 3619 AN: 152214 Hom.: 62 Cov.: 32 AF XY: 0.0233 AC XY: 1737 AN XY: 74412

African (AFR) AF: 0.00874 AC: 363 AN: 41536

American (AMR) AF: 0.0328 AC: 501 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0182 AC: 63 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.0235 AC: 113 AN: 4810

European-Finnish (FIN) AF: 0.0125 AC: 132 AN: 10600

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0346 AC: 2351 AN: 68016

Other (OTH) AF: 0.0341 AC: 72 AN: 2110

Alfa AF: 0.0287 Hom.: 37

Bravo AF: 0.0243

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	Congenital myasthenic syndrome 5 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.0
DANN	Benign	0.57
PhyloP100		2.5
Mutation Taster		=99/1	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: rs55866379; hg19: chr3-15495386;