NM_004393.6:c.1186A>G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004393.6(DAG1):c.1186A>G(p.Thr396Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,613,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_004393.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DAG1 | NM_004393.6 | c.1186A>G | p.Thr396Ala | missense_variant | Exon 3 of 3 | ENST00000308775.7 | NP_004384.5 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152066Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251426Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135872
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461774Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13AN XY: 727164
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152066Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74276
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.1186A>G (p.T396A) alteration is located in exon 3 (coding exon 2) of the DAG1 gene. This alteration results from a A to G substitution at nucleotide position 1186, causing the threonine (T) at amino acid position 396 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 21388311) -
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9;C4511963:Autosomal recessive limb-girdle muscular dystrophy type 2P Uncertain:1
This sequence change replaces threonine with alanine at codon 396 of the DAG1 protein (p.Thr396Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs779846682, ExAC 0.001%). This variant has not been reported in the literature in individuals with DAG1-related disease. 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 and their clinical significance is uncertain. 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