chr1-1049746-G-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_198576.4(AGRN):āc.4695G>Cā(p.Gln1565His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,579,520 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q1565R) has been classified as Likely benign.
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
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGRN | NM_198576.4 | c.4695G>C | p.Gln1565His | missense_variant | 26/36 | ENST00000379370.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGRN | ENST00000379370.7 | c.4695G>C | p.Gln1565His | missense_variant | 26/36 | 1 | NM_198576.4 | P1 | |
AGRN | ENST00000651234.1 | c.4380G>C | p.Gln1460His | missense_variant | 25/38 | ||||
AGRN | ENST00000652369.1 | c.4380G>C | p.Gln1460His | missense_variant | 25/35 | ||||
AGRN | ENST00000620552.4 | c.4281G>C | p.Gln1427His | missense_variant | 26/39 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00736 AC: 1111AN: 150896Hom.: 7 Cov.: 32
GnomAD3 exomes AF: 0.00177 AC: 328AN: 185194Hom.: 5 AF XY: 0.00115 AC XY: 117AN XY: 102010
GnomAD4 exome AF: 0.000715 AC: 1021AN: 1428506Hom.: 15 Cov.: 45 AF XY: 0.000575 AC XY: 407AN XY: 707854
GnomAD4 genome AF: 0.00736 AC: 1111AN: 151014Hom.: 7 Cov.: 32 AF XY: 0.00717 AC XY: 529AN XY: 73818
ClinVar
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 22, 2021 | - - |
AGRN-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 29, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Congenital myasthenic syndrome 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at