rs200051701
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_198576.4(AGRN):c.4924G>A(p.Gly1642Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00021 in 1,613,064 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 (★). Synonymous variant affecting the same amino acid position (i.e. G1642G) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGRN | NM_198576.4 | c.4924G>A | p.Gly1642Ser | missense_variant | 28/36 | ENST00000379370.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGRN | ENST00000379370.7 | c.4924G>A | p.Gly1642Ser | missense_variant | 28/36 | 1 | NM_198576.4 | P1 | |
AGRN | ENST00000651234.1 | c.4609G>A | p.Gly1537Ser | missense_variant | 27/38 | ||||
AGRN | ENST00000652369.1 | c.4609G>A | p.Gly1537Ser | missense_variant | 27/35 | ||||
AGRN | ENST00000620552.4 | c.4510G>A | p.Gly1504Ser | missense_variant | 28/39 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000790 AC: 12AN: 151982Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000108 AC: 27AN: 249770Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135478
GnomAD4 exome AF: 0.000224 AC: 327AN: 1460964Hom.: 0 Cov.: 34 AF XY: 0.000228 AC XY: 166AN XY: 726782
GnomAD4 genome ? AF: 0.0000789 AC: 12AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74370
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1642 of the AGRN protein (p.Gly1642Ser). This variant is present in population databases (rs200051701, 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: 572154). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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