1-1047588-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_198576.4(AGRN):c.3532C>T(p.Arg1178Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000471 in 1,612,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1178Q) has been classified as Likely benign.
Frequency
Consequence
NM_198576.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AGRN | NM_198576.4 | c.3532C>T | p.Arg1178Trp | missense_variant | 21/36 | ENST00000379370.7 | NP_940978.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AGRN | ENST00000379370.7 | c.3532C>T | p.Arg1178Trp | missense_variant | 21/36 | 1 | NM_198576.4 | ENSP00000368678.2 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152246Hom.: 0 Cov.: 36
GnomAD3 exomes AF: 0.0000360 AC: 9AN: 250124Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135664
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1460598Hom.: 0 Cov.: 80 AF XY: 0.0000399 AC XY: 29AN XY: 726590
GnomAD4 genome AF: 0.000118 AC: 18AN: 152364Hom.: 0 Cov.: 36 AF XY: 0.0000940 AC XY: 7AN XY: 74494
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jun 08, 2023 | BP4 - |
Congenital myasthenic syndrome 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 12, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1178 of the AGRN protein (p.Arg1178Trp). This variant is present in population databases (rs149268246, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with AGRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 570533). 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: "Benign"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at