chr11-36573341-T-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000448.3(RAG1):c.37T>G(p.Ser13Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,614,086 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
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAG1 | NM_000448.3 | c.37T>G | p.Ser13Ala | missense_variant | 2/2 | ENST00000299440.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAG1 | ENST00000299440.6 | c.37T>G | p.Ser13Ala | missense_variant | 2/2 | 1 | NM_000448.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000143 AC: 36AN: 251378Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135866
GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461888Hom.: 0 Cov.: 30 AF XY: 0.0000330 AC XY: 24AN XY: 727244
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
Recombinase activating gene 1 deficiency Uncertain:1
Uncertain significance, reviewed by expert panel | curation | ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen | Jan 24, 2024 | NM_000448.3(RAG1):c.37T>G is a missense variant predicted to cause substitution of Serine by Alanine at amino acid 13 (p.Ser13Ala). The highest population minor allele frequency in gnomAD v4 is 0.0007334 (44/59996) in Admixed American population (PM2_Supporting, BS1, and BA1 are not met).There are no publications for this variant in the literature. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal recessive severe combined immunodeficiency due to RAG1 deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: No criteria met (VCEP specifications version 1). - |
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Histiocytic medullary reticulosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive;C2673536:Combined immunodeficiency with skin granulomas Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at