2-74515204-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_016170.5(TLX2):c.398C>T(p.Thr133Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000174 in 1,540,194 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. 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. T133S) has been classified as Uncertain significance.
Frequency
Consequence
NM_016170.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TLX2 | ENST00000233638.8 | c.398C>T | p.Thr133Met | missense_variant, splice_region_variant | Exon 1 of 3 | 1 | NM_016170.5 | ENSP00000233638.6 | ||
TLX2 | ENST00000621092.1 | c.12-429C>T | intron_variant | Intron 2 of 3 | 1 | ENSP00000482690.1 | ||||
TLX2 | ENST00000497238.1 | n.704C>T | splice_region_variant, non_coding_transcript_exon_variant | Exon 3 of 4 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000122 AC: 17AN: 138974Hom.: 0 AF XY: 0.0000791 AC XY: 6AN XY: 75860
GnomAD4 exome AF: 0.000179 AC: 249AN: 1387974Hom.: 0 Cov.: 34 AF XY: 0.000163 AC XY: 112AN XY: 685340
GnomAD4 genome AF: 0.000125 AC: 19AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74374
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.398C>T (p.T133M) alteration is located in exon 1 (coding exon 1) of the TLX2 gene. This alteration results from a C to T substitution at nucleotide position 398, causing the threonine (T) at amino acid position 133 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at