rs759844691
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_198576.4(AGRN):c.1449C>T(p.Asn483=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,611,478 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
AGRN
NM_198576.4 synonymous
NM_198576.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.227
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 Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 1-1043303-C-T is Benign according to our data. Variant chr1-1043303-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 541184.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.227 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGRN | NM_198576.4 | c.1449C>T | p.Asn483= | synonymous_variant | 8/36 | ENST00000379370.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGRN | ENST00000379370.7 | c.1449C>T | p.Asn483= | synonymous_variant | 8/36 | 1 | NM_198576.4 | P1 | |
AGRN | ENST00000651234.1 | c.1134C>T | p.Asn378= | synonymous_variant | 7/38 | ||||
AGRN | ENST00000652369.1 | c.1134C>T | p.Asn378= | synonymous_variant | 7/35 | ||||
AGRN | ENST00000620552.4 | c.1035C>T | p.Asn345= | synonymous_variant | 8/39 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152182Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000369 AC: 9AN: 244162Hom.: 0 AF XY: 0.0000377 AC XY: 5AN XY: 132460
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1459296Hom.: 0 Cov.: 35 AF XY: 0.0000152 AC XY: 11AN XY: 725822
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GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74338
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital myasthenic syndrome 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 29, 2023 | - - |
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
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at