3-15451129-G-A

Variant names:

• chr3-15451129-G-A
• rs10154896
• NM_005677.4:c.*515C>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.*515C>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 0.0625 in 164,430 control chromosomes in the GnomAD database, including 577 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (560 hom., cov: 31)
  • Exomes 𝑓: 0.031 (17 hom.)
• Consequence: COLQ NM_005677.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.05
• Publications: 2 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-15451129-G-A is Benign according to our data. Variant chr3-15451129-G-A is described in ClinVar as Benign. ClinVar VariationId is 343835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 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.*515C>T		3_prime_UTR	Exon 17 of 17	NP_005668.2
	COLQ	NM_080538.2		c.*515C>T		3_prime_UTR	Exon 17 of 17	NP_536799.1	Q9Y215-2
	COLQ	NM_080539.4		c.*515C>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.*515C>T		3_prime_UTR	Exon 17 of 17	ENSP00000373298.3	Q9Y215-1
	ENSG00000293553	ENST00000629729.3	TSL:5	n.*291+316C>T		intron	N/A	ENSP00000518887.1	A0AAA9YHP9
	COLQ	ENST00000874202.1		c.*515C>T		3_prime_UTR	Exon 17 of 17	ENSP00000544261.1

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9879 AN: 151988 Hom.: 559 Cov.: 31

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0499

Gnomad ASJ AF: 0.0181

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.0684

GnomAD4 exome AF: 0.0315 AC: 388 AN: 12324 Hom.: 17 Cov.: 0 AF XY: 0.0323 AC XY: 215 AN XY: 6660

African (AFR) AF: 0.174 AC: 60 AN: 344

American (AMR) AF: 0.0268 AC: 56 AN: 2092

Ashkenazi Jewish (ASJ) AF: 0.00575 AC: 1 AN: 174

East Asian (EAS) AF: 0.00 AC: 0 AN: 876

South Asian (SAS) AF: 0.0364 AC: 44 AN: 1210

European-Finnish (FIN) AF: 0.0139 AC: 7 AN: 502

Middle Eastern (MID) AF: 0.0588 AC: 2 AN: 34

European-Non Finnish (NFE) AF: 0.0311 AC: 205 AN: 6586

Other (OTH) AF: 0.0257 AC: 13 AN: 506

GnomAD4 genome AF: 0.0650 AC: 9891 AN: 152106 Hom.: 560 Cov.: 31 AF XY: 0.0626 AC XY: 4652 AN XY: 74352

African (AFR) AF: 0.150 AC: 6218 AN: 41474

American (AMR) AF: 0.0499 AC: 762 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0181 AC: 63 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.0244 AC: 117 AN: 4802

European-Finnish (FIN) AF: 0.0126 AC: 134 AN: 10608

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0357 AC: 2425 AN: 67980

Other (OTH) AF: 0.0676 AC: 143 AN: 2114

Alfa AF: 0.0459 Hom.: 329

Bravo AF: 0.0718

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.90
CADD	Benign	0.55
DANN	Benign	0.62
PhyloP100		-1.1
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: rs10154896; hg19: chr3-15492636;