rs777215134

Variant names:

• chr3-15488285-T-C
• rs777215134
• NM_005677.4:c.242A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-15488285-T-C
• chr3-15488285-T-G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP2 BP4_Strong BS2

The NM_005677.4(COLQ):​c.242A>G​(p.Asn81Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,514 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N81D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00034 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: COLQ NM_005677.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:4
• Conservation: PhyloP100: 2.11
• 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)

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 16 curated pathogenic missense variants (we use a threshold of 10). The gene has 5 curated benign missense variants. Gene score misZ: -0.21928 (below the threshold of 3.09). Trascript score misZ: -0.17745 (below the threshold of 3.09). GenCC associations: The gene is linked to congenital myasthenic syndrome 5.
• BP4: Computational evidence support a benign effect (MetaRNN=0.009226531).
• BS2: High Homozygotes in GnomAd4 at 2 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.242A>G	p.Asn81Ser	missense	Exon 3 of 17	NP_005668.2
	COLQ	NM_080538.2		c.212A>G	p.Asn71Ser	missense	Exon 3 of 17	NP_536799.1	Q9Y215-2
	COLQ	NM_080539.4		c.219+1240A>G		intron	N/A	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.242A>G	p.Asn81Ser	missense	Exon 3 of 17	ENSP00000373298.3	Q9Y215-1
	COLQ	ENST00000603808.5	TSL:1	c.242A>G	p.Asn81Ser	missense	Exon 3 of 17	ENSP00000474271.1	A0A0C4DGS2
	COLQ	ENST00000874202.1		c.242A>G	p.Asn81Ser	missense	Exon 3 of 17	ENSP00000544261.1

Frequencies

GnomAD3 genomes AF: 0.000335 AC: 51 AN: 152162 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250510 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461352 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727002

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111962

Other (OTH) AF: 0.0000331 AC: 2 AN: 60392

GnomAD4 genome AF: 0.000335 AC: 51 AN: 152162 Hom.: 2 Cov.: 32 AF XY: 0.000336 AC XY: 25 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000510

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	3	-	Congenital myasthenic syndrome 5 (3)
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.85	D
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.0092	T
MetaSVM	Uncertain	0.59	D
MutationAssessor	Benign	1.1	L
PhyloP100		2.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.026	D
Sift4G	Benign	0.76	T
Polyphen		0.93	P
Vest4		0.17
MutPred		0.43		Gain of phosphorylation at N81 (P = 0.0197)
MVP		0.95
MPC		0.42
ClinPred		0.37	T
GERP RS		4.9
Varity_R		0.081
gMVP		0.14
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs777215134; hg19: chr3-15529792;