rs149636063
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_198576.4(AGRN):c.1198C>A(p.Arg400=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,611,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
AGRN
NM_198576.4 synonymous
NM_198576.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.489
Genes affected
AGRN (HGNC:329): (agrin) This gene encodes one of several proteins that are critical in the development of the neuromuscular junction (NMJ), as identified in mouse knock-out studies. The encoded protein contains several laminin G, Kazal type serine protease inhibitor, and epidermal growth factor domains. Additional post-translational modifications occur to add glycosaminoglycans and disulfide bonds. In one family with congenital myasthenic syndrome affecting limb-girdle muscles, a mutation in this gene was found. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| AGRN | NM_198576.4 | c.1198C>A | p.Arg400= | synonymous_variant | 7/36 | ENST00000379370.7 | NP_940978.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| AGRN | ENST00000379370.7 | c.1198C>A | p.Arg400= | synonymous_variant | 7/36 | 1 | NM_198576.4 | ENSP00000368678 | P1 | |
| AGRN | ENST00000651234.1 | c.883C>A | p.Arg295= | synonymous_variant | 6/38 | ENSP00000499046 | ||||
| AGRN | ENST00000652369.1 | c.883C>A | p.Arg295= | synonymous_variant | 6/35 | ENSP00000498543 | ||||
| AGRN | ENST00000620552.4 | c.784C>A | p.Arg262= | synonymous_variant | 7/39 | 5 | ENSP00000484607 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 34
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459494Hom.: 0 Cov.: 77 AF XY: 0.00000275 AC XY: 2AN XY: 726134
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GnomAD4 genome 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74332
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Not reported inComputational scores
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Benign
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Benign
RBP_binding_hub_radar
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at