rs754179635
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_144670.6(A2ML1):āc.2379C>Gā(p.Asp793Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_144670.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
A2ML1 | NM_144670.6 | c.2379C>G | p.Asp793Glu | missense_variant | 19/36 | ENST00000299698.12 | NP_653271.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
A2ML1 | ENST00000299698.12 | c.2379C>G | p.Asp793Glu | missense_variant | 19/36 | 1 | NM_144670.6 | ENSP00000299698.7 | ||
A2ML1 | ENST00000541459.5 | c.1029C>G | p.Asp343Glu | missense_variant | 8/25 | 2 | ENSP00000443174.1 | |||
A2ML1 | ENST00000539547.5 | c.906C>G | p.Asp302Glu | missense_variant | 8/25 | 2 | ENSP00000438292.1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249564Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135396
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461888Hom.: 0 Cov.: 37 AF XY: 0.0000165 AC XY: 12AN XY: 727246
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74326
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 17, 2024 | The p.D793E variant (also known as c.2379C>G), located in coding exon 19 of the A2ML1 gene, results from a C to G substitution at nucleotide position 2379. The aspartic acid at codon 793 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 25, 2016 | In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant is present in population databases (rs754179635, ExAC <0.01%) but has not been reported in the literature in individuals with a A2ML1-related disease. This sequence change replaces aspartic acid with glutamic acid at codon 793 of the A2ML1 protein (p.Asp793Glu). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at