3-49510557-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004393.6(DAG1):c.23C>T(p.Ser8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,626 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 (★★). Synonymous variant affecting the same amino acid position (i.e. S8S) has been classified as Likely benign.
Frequency
Consequence
NM_004393.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DAG1 | NM_004393.6 | c.23C>T | p.Ser8Leu | missense_variant | 2/3 | ENST00000308775.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DAG1 | ENST00000308775.7 | c.23C>T | p.Ser8Leu | missense_variant | 2/3 | 1 | NM_004393.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152012Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250510Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135374
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461496Hom.: 0 Cov.: 29 AF XY: 0.0000151 AC XY: 11AN XY: 727040
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74360
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 20, 2021 | The c.23C>T (p.S8L) alteration is located in exon 2 (coding exon 1) of the DAG1 gene. This alteration results from a C to T substitution at nucleotide position 23, causing the serine (S) at amino acid position 8 to be replaced by a leucine (L). 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 | Revvity Omics, Revvity | May 25, 2023 | - - |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9;C4511963:Autosomal recessive limb-girdle muscular dystrophy type 2P Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces serine with leucine at codon 8 of the DAG1 protein (p.Ser8Leu). The serine residue is weakly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs199501149, ExAC 0.005%). This variant has not been reported in the literature in individuals affected with DAG1-related conditions. 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 leucine 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at