rs755427684
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_198576.4(AGRN):c.3803G>A(p.Gly1268Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000305 in 1,585,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGRN | NM_198576.4 | c.3803G>A | p.Gly1268Glu | missense_variant | 23/36 | ENST00000379370.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGRN | ENST00000379370.7 | c.3803G>A | p.Gly1268Glu | missense_variant | 23/36 | 1 | NM_198576.4 | P1 | |
AGRN | ENST00000651234.1 | c.3488G>A | p.Gly1163Glu | missense_variant | 22/38 | ||||
AGRN | ENST00000652369.1 | c.3488G>A | p.Gly1163Glu | missense_variant | 22/35 | ||||
AGRN | ENST00000620552.4 | c.3389G>A | p.Gly1130Glu | missense_variant | 23/39 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152098Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000224 AC: 46AN: 205072Hom.: 0 AF XY: 0.000239 AC XY: 27AN XY: 112924
GnomAD4 exome AF: 0.000318 AC: 455AN: 1432816Hom.: 0 Cov.: 36 AF XY: 0.000281 AC XY: 200AN XY: 711702
GnomAD4 genome ? AF: 0.000191 AC: 29AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74432
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 05, 2022 | The c.3803G>A (p.G1268E) alteration is located in exon 23 (coding exon 23) of the AGRN gene. This alteration results from a G to A substitution at nucleotide position 3803, causing the glycine (G) at amino acid position 1268 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Congenital myasthenic syndrome 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 1268 of the AGRN protein (p.Gly1268Glu). This variant is present in population databases (rs755427684, gnomAD 0.06%). 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: 569151). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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