rs1553634628

Variant names:

• chr3-15455974-T-A
• rs1553634628
• NM_005677.4:c.1120A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-15455974-T-A
• chr3-15455974-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_005677.4(COLQ):​c.1120A>T​(p.Thr374Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T374P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: COLQ NM_005677.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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=0.17794862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COLQ	NM_005677.4	c.1120A>T	p.Thr374Ser	missense_variant	Exon 15 of 17	ENST00000383788.10	NP_005668.2
COLQ	NM_080538.2	c.1090A>T	p.Thr364Ser	missense_variant	Exon 15 of 17		NP_536799.1
COLQ	NM_080539.4	c.1018A>T	p.Thr340Ser	missense_variant	Exon 14 of 16		NP_536800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COLQ	ENST00000383788.10	c.1120A>T	p.Thr374Ser	missense_variant	Exon 15 of 17	1	NM_005677.4	ENSP00000373298.3
COLQ	ENST00000603808.5	c.1120A>T	p.Thr374Ser	missense_variant	Exon 15 of 17	1		ENSP00000474271.1
ENSG00000293553	ENST00000629729.3	n.-34A>T		upstream_gene_variant		5		ENSP00000518887.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461812 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33478

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: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	8.5
DANN	Benign	0.77
DEOGEN2	Benign	0.21	T;.;.;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.69	T;T;T;T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	-0.34	N;.;.;.
PhyloP100		0.26
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.70	N;N;.;N
REVEL	Benign	0.20
Sift	Benign	0.50	T;T;.;.
Sift4G	Benign	0.46	T;T;T;T
Polyphen		0.017	B;B;.;B
Vest4		0.21
MutPred		0.47		Gain of disorder (P = 0.0486);.;Gain of disorder (P = 0.0486);.;
MVP		0.84
MPC		0.087
ClinPred		0.13	T
GERP RS		1.7
Varity_R		0.036
gMVP		0.35
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1553634628; hg19: chr3-15497481;