rs750324839

Variant names:

• chr3-15475436-T-A
• NM_005677.4:c.517A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-15475436-T-A
• chr3-15475436-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005677.4(COLQ):​c.517A>T​(p.Met173Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,447,424 control chromosomes in the GnomAD database, with no homozygous occurrence. 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.

• 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: 1.11

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2851319).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COLQ	NM_005677.4	c.517A>T	p.Met173Leu	missense_variant	Exon 7 of 17	ENST00000383788.10	NP_005668.2
COLQ	NM_080538.2	c.487A>T	p.Met163Leu	missense_variant	Exon 7 of 17		NP_536799.1
COLQ	NM_080539.4	c.415A>T	p.Met139Leu	missense_variant	Exon 6 of 16		NP_536800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COLQ	ENST00000383788.10	c.517A>T	p.Met173Leu	missense_variant	Exon 7 of 17	1	NM_005677.4	ENSP00000373298.3
COLQ	ENST00000603808.5	c.517A>T	p.Met173Leu	missense_variant	Exon 7 of 17	1		ENSP00000474271.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1447424 Hom.: 0 Cov.: 34 AF XY: 0.00000278 AC XY: 2 AN XY: 718316

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	15
DANN	Benign	0.76
DEOGEN2	Benign	0.29	T;.;.;.;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.77	T;T;T;T;T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.29	T;T;T;T;T
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	0.40	N;.;.;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.96	N;N;.;N;.
REVEL	Benign	0.23
Sift	Benign	0.13	T;T;.;.;.
Sift4G	Benign	0.30	T;T;T;T;T
Polyphen		0.19	B;P;.;B;.
Vest4		0.37
MutPred		0.31		Loss of MoRF binding (P = 0.0751);.;Loss of MoRF binding (P = 0.0751);.;.;
MVP		0.63
MPC		0.091
ClinPred		0.41	T
GERP RS		0.43
Varity_R		0.22
gMVP		0.062

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-15516943;