rs146154694
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_000642.3(AGL):āc.4300A>Gā(p.Asn1434Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000893 in 1,612,668 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 Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1434S) has been classified as Uncertain significance.
Frequency
Consequence
NM_000642.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AGL | NM_000642.3 | c.4300A>G | p.Asn1434Asp | missense_variant | 32/34 | ENST00000361915.8 | NP_000633.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152240Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000599 AC: 15AN: 250442Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135368
GnomAD4 exome AF: 0.0000938 AC: 137AN: 1460428Hom.: 0 Cov.: 31 AF XY: 0.0000771 AC XY: 56AN XY: 726510
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74380
ClinVar
Submissions by phenotype
Glycogen storage disease type III Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 21, 2022 | This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 1434 of the AGL protein (p.Asn1434Asp). This variant is present in population databases (rs146154694, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with AGL-related conditions. ClinVar contains an entry for this variant (Variation ID: 456503). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 26, 2024 | The c.4300A>G (p.N1434D) alteration is located in exon 32 (coding exon 31) of the AGL gene. This alteration results from a A to G substitution at nucleotide position 4300, causing the asparagine (N) at amino acid position 1434 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jun 08, 2022 | BP4, PM2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at