3-15453879-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005677.4(COLQ):​c.1248C>A​(p.Asp416Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D416D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COLQ NM_005677.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50

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]

EAF1-AS1 (HGNC:42328): (EAF1 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23930779).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COLQ	NM_005677.4	c.1248C>A	p.Asp416Glu	missense_variant	Exon 16 of 17	ENST00000383788.10	NP_005668.2
COLQ	NM_080538.2	c.1218C>A	p.Asp406Glu	missense_variant	Exon 16 of 17		NP_536799.1
COLQ	NM_080539.4	c.1146C>A	p.Asp382Glu	missense_variant	Exon 15 of 16		NP_536800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COLQ	ENST00000383788.10	c.1248C>A	p.Asp416Glu	missense_variant	Exon 16 of 17	1	NM_005677.4	ENSP00000373298.3
COLQ	ENST00000603808.5	c.1251C>A	p.Asp417Glu	missense_variant	Exon 16 of 17	1		ENSP00000474271.1
EAF1-AS1	ENST00000629729.2	n.95C>A		non_coding_transcript_exon_variant	Exon 2 of 6	5		ENSP00000518887.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.14	T;.;.;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.81	T;T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	0.53	N;.;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.11	N;N;.;N
REVEL	Benign	0.15
Sift	Benign	0.40	T;T;.;.
Sift4G	Benign	0.91	T;T;T;T
Polyphen		0.28	B;B;.;B
Vest4		0.27
MutPred		0.21		Loss of sheet (P = 0.1398);.;.;.;
MVP		0.95
MPC		0.091
ClinPred		0.35	T
GERP RS		3.4
Varity_R		0.054
gMVP		0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs55866379; hg19: chr3-15495386;