rs746295635
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_017872.5(THG1L):c.137C>A(p.Thr46Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000168 in 1,611,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T46S) has been classified as Uncertain significance.
Frequency
Consequence
NM_017872.5 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 |
---|---|---|---|---|---|---|---|
THG1L | NM_017872.5 | c.137C>A | p.Thr46Asn | missense_variant | 1/6 | ENST00000231198.12 | |
THG1L | NM_001317824.2 | c.-165C>A | 5_prime_UTR_variant | 1/6 | |||
THG1L | NM_001317825.2 | c.-235C>A | 5_prime_UTR_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THG1L | ENST00000231198.12 | c.137C>A | p.Thr46Asn | missense_variant | 1/6 | 1 | NM_017872.5 | P1 | |
THG1L | ENST00000521655.1 | c.137C>A | p.Thr46Asn | missense_variant, NMD_transcript_variant | 1/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152250Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1459262Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 725884
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74374
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 02, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 16, 2021 | In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28097321) - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 20, 2021 | The c.137C>A (p.T46N) alteration is located in coding exon 1 of the THG1L gene. This alteration results from a C to A substitution at nucleotide position 137, causing the threonine (T) at amino acid position 46 to be replaced by an asparagine (N). Based on data from the Genome Aggregation Database (gnomAD), the THG1L c.137C>A alteration was observed in 0.006% (2/31406) of total alleles studied, with a frequency of 0.013% (2/15432) in the European (non-Finnish) subpopulation. This alteration has been observed homozygous in two first cousins from one family who presented with mild intellectual disability and ataxia (Reuter, 2017). This amino acid position is highly conserved in available vertebrate species. The p.T46N alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Spinocerebellar ataxia, autosomal recessive 28 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Mar 01, 2020 | Review of the variants reported in Reuter et al., 2017, PMID: 28097321: PM2,PM3_Supporting - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at