rs756710837
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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):āc.519G>Cā(p.Arg173=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 1,547,564 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 (ā ).
Frequency
Genomes: š 0.00018 ( 0 hom., cov: 29)
Exomes š: 0.000012 ( 0 hom. )
Consequence
AGRN
NM_198576.4 synonymous
NM_198576.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0960
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=-0.62).
BP6
?
Variant 1-1040672-G-C is Benign according to our data. Variant chr1-1040672-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 541188.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.096 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGRN | NM_198576.4 | c.519G>C | p.Arg173= | synonymous_variant | 4/36 | ENST00000379370.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGRN | ENST00000379370.7 | c.519G>C | p.Arg173= | synonymous_variant | 4/36 | 1 | NM_198576.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000178 AC: 27AN: 152036Hom.: 0 Cov.: 29
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GnomAD3 exomes AF: 0.0000547 AC: 8AN: 146288Hom.: 0 AF XY: 0.0000381 AC XY: 3AN XY: 78790
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GnomAD4 exome AF: 0.0000122 AC: 17AN: 1395528Hom.: 0 Cov.: 33 AF XY: 0.00000726 AC XY: 5AN XY: 688366
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GnomAD4 genome ? AF: 0.000178 AC: 27AN: 152036Hom.: 0 Cov.: 29 AF XY: 0.000242 AC XY: 18AN XY: 74252
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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 | Aug 09, 2023 | - - |
Computational scores
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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