rs1008156537
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_005677.4(COLQ):c.1162G>A(p.Asp388Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D388D) has been classified as Likely benign.
Frequency
Consequence
NM_005677.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COLQ | NM_005677.4 | c.1162G>A | p.Asp388Asn | missense_variant | 15/17 | ENST00000383788.10 | |
COLQ | NM_080538.2 | c.1132G>A | p.Asp378Asn | missense_variant | 15/17 | ||
COLQ | NM_080539.4 | c.1060G>A | p.Asp354Asn | missense_variant | 14/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COLQ | ENST00000383788.10 | c.1162G>A | p.Asp388Asn | missense_variant | 15/17 | 1 | NM_005677.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251264Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135796
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461872Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727236
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 5 Pathogenic:1Uncertain:1
Likely pathogenic, no assertion criteria provided | clinical testing | Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust | May 03, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 06, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 388 of the COLQ protein (p.Asp388Asn). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 468340). This variant is also known as p.Asp354Asn. This missense change has been observed in individual(s) with clinical features of COLQ-related conditions (PMID: 31345272). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at