rs375727924
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_003235.5(TG):c.3397G>A(p.Glu1133Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_003235.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TG | NM_003235.5 | c.3397G>A | p.Glu1133Lys | missense_variant | 15/48 | ENST00000220616.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TG | ENST00000220616.9 | c.3397G>A | p.Glu1133Lys | missense_variant | 15/48 | 1 | NM_003235.5 | P1 | |
TG | ENST00000523756.5 | c.289+1393G>A | intron_variant, NMD_transcript_variant | 1 | |||||
TG | ENST00000518505.1 | c.298G>A | p.Glu100Lys | missense_variant | 4/6 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000280 AC: 7AN: 250050Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135212
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461608Hom.: 0 Cov.: 31 AF XY: 0.0000426 AC XY: 31AN XY: 727042
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74356
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 07, 2016 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 09, 2024 | The c.3397G>A (p.E1133K) alteration is located in exon 15 (coding exon 15) of the TG gene. This alteration results from a G to A substitution at nucleotide position 3397, causing the glutamic acid (E) at amino acid position 1133 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Iodotyrosyl coupling defect 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at