X-101020588-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_024917.6(TRMT2B):c.1067G>A(p.Gly356Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000253 in 1,183,951 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_024917.6 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRMT2B | NM_024917.6 | c.1067G>A | p.Gly356Asp | missense_variant, splice_region_variant | Exon 11 of 14 | ENST00000372936.4 | NP_079193.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRMT2B | ENST00000372936.4 | c.1067G>A | p.Gly356Asp | missense_variant, splice_region_variant | Exon 11 of 14 | 1 | NM_024917.6 | ENSP00000362027.3 | ||
TRMT2B | ENST00000372935.5 | c.1067G>A | p.Gly356Asp | missense_variant, splice_region_variant | Exon 11 of 14 | 1 | ENSP00000362026.1 | |||
TRMT2B | ENST00000545398.5 | c.1067G>A | p.Gly356Asp | missense_variant, splice_region_variant | Exon 10 of 13 | 1 | ENSP00000438134.1 | |||
TRMT2B | ENST00000372939.5 | c.932G>A | p.Gly311Asp | missense_variant, splice_region_variant | Exon 11 of 14 | 1 | ENSP00000362030.1 |
Frequencies
GnomAD3 genomes AF: 0.00000893 AC: 1AN: 111983Hom.: 0 Cov.: 23 AF XY: 0.0000292 AC XY: 1AN XY: 34205
GnomAD4 exome AF: 0.00000187 AC: 2AN: 1071968Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0AN XY: 338754
GnomAD4 genome AF: 0.00000893 AC: 1AN: 111983Hom.: 0 Cov.: 23 AF XY: 0.0000292 AC XY: 1AN XY: 34205
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1067G>A (p.G356D) alteration is located in exon 11 (coding exon 9) of the TRMT2B gene. This alteration results from a G to A substitution at nucleotide position 1067, causing the glycine (G) at amino acid position 356 to be replaced by an aspartic acid (D). 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