chr11-36573344-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000448.3(RAG1):c.40G>A(p.Ala14Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 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_000448.3 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAG1 | NM_000448.3 | c.40G>A | p.Ala14Thr | missense_variant | 2/2 | ENST00000299440.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAG1 | ENST00000299440.6 | c.40G>A | p.Ala14Thr | missense_variant | 2/2 | 1 | NM_000448.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251368Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135862
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461888Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727246
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 27, 2023 | The c.40G>A (p.A14T) alteration is located in exon 2 (coding exon 1) of the RAG1 gene. This alteration results from a G to A substitution at nucleotide position 40, causing the alanine (A) at amino acid position 14 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;C2673536:Combined immunodeficiency with skin granulomas Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 19, 2022 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RAG1 protein function. This variant has not been reported in the literature in individuals affected with RAG1-related conditions. This variant is present in population databases (rs765396585, gnomAD 0.0009%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 14 of the RAG1 protein (p.Ala14Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at