rs140670616

Variant names:

• chr3-15453922-C-A
• NM_005677.4:c.1205G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-15453922-C-A
• chr3-15453922-C-G
• chr3-15453922-C-T

Variant summary

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

The NM_005677.4(COLQ):​c.1205G>T​(p.Arg402Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,868 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: COLQ NM_005677.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COLQ	NM_005677.4	c.1205G>T	p.Arg402Leu	missense_variant	Exon 16 of 17	ENST00000383788.10	NP_005668.2
COLQ	NM_080538.2	c.1175G>T	p.Arg392Leu	missense_variant	Exon 16 of 17		NP_536799.1
COLQ	NM_080539.4	c.1103G>T	p.Arg368Leu	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.1205G>T	p.Arg402Leu	missense_variant	Exon 16 of 17	1	NM_005677.4	ENSP00000373298.3
COLQ	ENST00000603808.5	c.1208G>T	p.Arg403Leu	missense_variant	Exon 16 of 17	1		ENSP00000474271.1
EAF1-AS1	ENST00000629729.2	n.52G>T		non_coding_transcript_exon_variant	Exon 2 of 6	5		ENSP00000518887.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1454868 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2 AN XY: 723300

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: 0.0000354

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T;.;.;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Uncertain	0.29	D
MetaRNN	Uncertain	0.68	D;D;D;D
MetaSVM	Uncertain	0.62	D
MutationAssessor	Uncertain	2.0	M;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.1	N;D;.;N
REVEL	Uncertain	0.64
Sift	Uncertain	0.0030	D;D;.;.
Sift4G	Benign	0.16	T;T;T;T
Polyphen		0.99	D;D;.;D
Vest4		0.63
MutPred		0.59		Loss of disorder (P = 0.0362);.;.;.;
MVP		0.95
MPC		0.12
ClinPred		0.89	D
GERP RS		4.7
Varity_R		0.21
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr3-15495429;