1-1041648-G-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_198576.4(AGRN):c.1123G>T(p.Ala375Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00657 in 1,611,148 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A375T) has been classified as Uncertain significance.
Frequency
Consequence
NM_198576.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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AGRN | ENST00000379370.7 | c.1123G>T | p.Ala375Ser | missense_variant | Exon 6 of 36 | 1 | NM_198576.4 | ENSP00000368678.2 | ||
AGRN | ENST00000651234.1 | c.808G>T | p.Ala270Ser | missense_variant | Exon 5 of 38 | ENSP00000499046.1 | ||||
AGRN | ENST00000652369.1 | c.808G>T | p.Ala270Ser | missense_variant | Exon 5 of 35 | ENSP00000498543.1 | ||||
AGRN | ENST00000620552.4 | c.709G>T | p.Ala237Ser | missense_variant | Exon 6 of 39 | 5 | ENSP00000484607.1 |
Frequencies
GnomAD3 genomes AF: 0.00518 AC: 787AN: 152064Hom.: 2 Cov.: 31
GnomAD3 exomes AF: 0.00493 AC: 1175AN: 238246Hom.: 4 AF XY: 0.00520 AC XY: 683AN XY: 131312
GnomAD4 exome AF: 0.00671 AC: 9794AN: 1458968Hom.: 36 Cov.: 33 AF XY: 0.00666 AC XY: 4836AN XY: 725714
GnomAD4 genome AF: 0.00518 AC: 788AN: 152180Hom.: 2 Cov.: 31 AF XY: 0.00458 AC XY: 341AN XY: 74408
ClinVar
Submissions by phenotype
not provided Benign:5
This variant is associated with the following publications: (PMID: 27378695) -
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AGRN: BS2 -
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not specified Benign:3
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Congenital myasthenic syndrome 8 Benign:2
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This variant is interpreted as Benign, for Myasthenic syndrome, congenital, 8, autosomal recessive. The following ACMG Tag(s) were applied: BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at