rs144164397
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP6BS1
The NM_198576.4(AGRN):c.1570C>T(p.Arg524Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000225 in 1,607,190 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R524Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_198576.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGRN | NM_198576.4 | c.1570C>T | p.Arg524Trp | missense_variant | 8/36 | ENST00000379370.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGRN | ENST00000379370.7 | c.1570C>T | p.Arg524Trp | missense_variant | 8/36 | 1 | NM_198576.4 | P1 | |
AGRN | ENST00000651234.1 | c.1255C>T | p.Arg419Trp | missense_variant | 7/38 | ||||
AGRN | ENST00000652369.1 | c.1255C>T | p.Arg419Trp | missense_variant | 7/35 | ||||
AGRN | ENST00000620552.4 | c.1156C>T | p.Arg386Trp | missense_variant | 8/39 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00110 AC: 167AN: 151952Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000277 AC: 65AN: 235044Hom.: 0 AF XY: 0.000211 AC XY: 27AN XY: 128156
GnomAD4 exome AF: 0.000134 AC: 195AN: 1455120Hom.: 0 Cov.: 35 AF XY: 0.000122 AC XY: 88AN XY: 723828
GnomAD4 genome AF: 0.00110 AC: 167AN: 152070Hom.: 0 Cov.: 33 AF XY: 0.00116 AC XY: 86AN XY: 74362
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 12, 2016 | - - |
AGRN-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 20, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Congenital myasthenic syndrome 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at