chr22-40156118-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_001024843.2(TNRC6B):c.49G>T(p.Glu17*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000019 in 1,577,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_001024843.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TNRC6B | NM_001024843.2 | c.49G>T | p.Glu17* | stop_gained | Exon 4 of 24 | NP_001020014.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TNRC6B | ENST00000402203.5 | c.49G>T | p.Glu17* | stop_gained | Exon 4 of 24 | 1 | ENSP00000384795.1 | |||
TNRC6B | ENST00000301923.13 | c.49G>T | p.Glu17* | stop_gained | Exon 4 of 24 | 5 | ENSP00000306759.9 | |||
TNRC6B | ENST00000441751.5 | c.49G>T | p.Glu17* | stop_gained | Exon 4 of 4 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000140 AC: 2AN: 1425574Hom.: 0 Cov.: 30 AF XY: 0.00000284 AC XY: 2AN XY: 705226
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74372
ClinVar
Submissions by phenotype
Global developmental delay with speech and behavioral abnormalities Pathogenic:1
This variant lies in exon 4 of the TNRC6B gene and is predicted to cause a premature termination of the protein (p.Glu17Ter). The resultant protein will likely to lack RRM domain, silencing domain, argonaute protein interacting region and PABPC1-interacting motif-2 of the protein [UniProt]; this will likely result in loss-of-function. Moreover, due to the introduction of a premature stop codon, this aberrant transcript will likely be targeted by the nonsense-mediated mRNA decay (NMD) mechanism [PMID: 15040442]. The variant seems to be a novel variant, as it has not been previously reported in population databases or in the literature. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at