chr1-1020177-C-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_198576.4(AGRN):c.5C>A(p.Ala2Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,334,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_198576.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AGRN | NM_198576.4 | c.5C>A | p.Ala2Asp | missense_variant | 1/36 | ENST00000379370.7 | NP_940978.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AGRN | ENST00000379370.7 | c.5C>A | p.Ala2Asp | missense_variant | 1/36 | 1 | NM_198576.4 | ENSP00000368678 | P1 | |
AGRN | ENST00000620552.4 | c.-410C>A | 5_prime_UTR_variant | 1/39 | 5 | ENSP00000484607 |
Frequencies
GnomAD3 genomes AF: 0.000922 AC: 139AN: 150818Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000165 AC: 5AN: 30378Hom.: 0 AF XY: 0.000109 AC XY: 2AN XY: 18430
GnomAD4 exome AF: 0.0000592 AC: 70AN: 1183116Hom.: 0 Cov.: 28 AF XY: 0.0000484 AC XY: 28AN XY: 578676
GnomAD4 genome AF: 0.000928 AC: 140AN: 150924Hom.: 0 Cov.: 31 AF XY: 0.000773 AC XY: 57AN XY: 73742
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 15, 2024 | This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 2 of the AGRN protein (p.Ala2Asp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with AGRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 474165). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at