rs149159118
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_198576.4(AGRN):c.3353C>A(p.Thr1118Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,579,524 control chromosomes in the GnomAD database, including 2 homozygotes. 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. T1118M) 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 -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGRN | NM_198576.4 | c.3353C>A | p.Thr1118Lys | missense_variant | 19/36 | ENST00000379370.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGRN | ENST00000379370.7 | c.3353C>A | p.Thr1118Lys | missense_variant | 19/36 | 1 | NM_198576.4 | P1 | |
AGRN | ENST00000651234.1 | c.3038C>A | p.Thr1013Lys | missense_variant | 18/38 | ||||
AGRN | ENST00000652369.1 | c.3038C>A | p.Thr1013Lys | missense_variant | 18/35 | ||||
AGRN | ENST00000620552.4 | c.2939C>A | p.Thr980Lys | missense_variant | 19/39 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00183 AC: 279AN: 152172Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.00187 AC: 356AN: 190804Hom.: 0 AF XY: 0.00190 AC XY: 194AN XY: 102348
GnomAD4 exome AF: 0.00198 AC: 2824AN: 1427234Hom.: 1 Cov.: 39 AF XY: 0.00192 AC XY: 1354AN XY: 706762
GnomAD4 genome AF: 0.00183 AC: 279AN: 152290Hom.: 1 Cov.: 33 AF XY: 0.00228 AC XY: 170AN XY: 74456
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 09, 2021 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 24951643, 26290588) - |
Congenital myasthenic syndrome 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 26, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at