chr1-1048116-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_198576.4(AGRN):c.3856C>T(p.Pro1286Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000424 in 1,416,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1286T) has been classified 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 | UniProt |
---|---|---|---|---|---|---|---|
AGRN | NM_198576.4 | c.3856C>T | p.Pro1286Ser | missense_variant | 23/36 | ENST00000379370.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGRN | ENST00000379370.7 | c.3856C>T | p.Pro1286Ser | missense_variant | 23/36 | 1 | NM_198576.4 | P1 | |
AGRN | ENST00000651234.1 | c.3541C>T | p.Pro1181Ser | missense_variant | 22/38 | ||||
AGRN | ENST00000652369.1 | c.3541C>T | p.Pro1181Ser | missense_variant | 22/35 | ||||
AGRN | ENST00000620552.4 | c.3442C>T | p.Pro1148Ser | missense_variant | 23/39 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000222 AC: 4AN: 179912Hom.: 0 AF XY: 0.0000203 AC XY: 2AN XY: 98352
GnomAD4 exome AF: 0.00000424 AC: 6AN: 1416738Hom.: 0 Cov.: 36 AF XY: 0.00000285 AC XY: 2AN XY: 702428
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 14, 2022 | The c.3856C>T (p.P1286S) alteration is located in exon 23 (coding exon 23) of the AGRN gene. This alteration results from a C to T substitution at nucleotide position 3856, causing the proline (P) at amino acid position 1286 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at