rs201166586
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_198576.4(AGRN):c.3276C>T(p.Ser1092=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 1,585,974 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00048 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00023 ( 4 hom. )
Consequence
AGRN
NM_198576.4 synonymous
NM_198576.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.885
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 Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 1-1046845-C-T is Benign according to our data. Variant chr1-1046845-C-T is described in ClinVar as [Benign]. Clinvar id is 474115.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.885 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000479 (73/152294) while in subpopulation EAS AF= 0.0108 (56/5186). AF 95% confidence interval is 0.00854. There are 0 homozygotes in gnomad4. There are 48 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGRN | NM_198576.4 | c.3276C>T | p.Ser1092= | synonymous_variant | 19/36 | ENST00000379370.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGRN | ENST00000379370.7 | c.3276C>T | p.Ser1092= | synonymous_variant | 19/36 | 1 | NM_198576.4 | P1 | |
AGRN | ENST00000651234.1 | c.2961C>T | p.Ser987= | synonymous_variant | 18/38 | ||||
AGRN | ENST00000652369.1 | c.2961C>T | p.Ser987= | synonymous_variant | 18/35 | ||||
AGRN | ENST00000620552.4 | c.2862C>T | p.Ser954= | synonymous_variant | 19/39 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000486 AC: 74AN: 152176Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000916 AC: 184AN: 200874Hom.: 2 AF XY: 0.000891 AC XY: 97AN XY: 108886
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GnomAD4 exome AF: 0.000228 AC: 327AN: 1433680Hom.: 4 Cov.: 39 AF XY: 0.000232 AC XY: 165AN XY: 710912
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GnomAD4 genome ? AF: 0.000479 AC: 73AN: 152294Hom.: 0 Cov.: 33 AF XY: 0.000645 AC XY: 48AN XY: 74474
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital myasthenic syndrome 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at