rs1235929400
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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.651C>T(p.Tyr217=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000195 in 1,538,950 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 0.000013 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
AGRN
NM_198576.4 synonymous
NM_198576.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.70
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=-0.56).
BP6
?
Variant 1-1040804-C-T is Benign according to our data. Variant chr1-1040804-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 541197.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.7 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGRN | NM_198576.4 | c.651C>T | p.Tyr217= | synonymous_variant | 4/36 | ENST00000379370.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGRN | ENST00000379370.7 | c.651C>T | p.Tyr217= | synonymous_variant | 4/36 | 1 | NM_198576.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151574Hom.: 0 Cov.: 29
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GnomAD4 exome AF: 0.0000202 AC: 28AN: 1387376Hom.: 0 Cov.: 33 AF XY: 0.0000234 AC XY: 16AN XY: 685152
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151574Hom.: 0 Cov.: 29 AF XY: 0.0000270 AC XY: 2AN XY: 74014
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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 | Jan 24, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_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