14-55424252-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_199047.3(TBPL2):āc.862T>Cā(p.Tyr288His) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,452,324 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (ā ).
Frequency
Consequence
NM_199047.3 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBPL2 | NM_199047.3 | c.862T>C | p.Tyr288His | missense_variant, splice_region_variant | 6/7 | ENST00000247219.6 | |
FBXO34 | XR_007064022.1 | n.2982+168A>G | intron_variant, non_coding_transcript_variant | ||||
FBXO34 | XR_007064023.1 | n.2941-18575A>G | intron_variant, non_coding_transcript_variant | ||||
FBXO34 | XR_007064024.1 | n.2982+168A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBPL2 | ENST00000247219.6 | c.862T>C | p.Tyr288His | missense_variant, splice_region_variant | 6/7 | 1 | NM_199047.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250218Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135252
GnomAD4 exome AF: 0.00000207 AC: 3AN: 1452324Hom.: 0 Cov.: 27 AF XY: 0.00000277 AC XY: 2AN XY: 722976
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 17, 2023 | The c.958T>C (p.Y320H) alteration is located in exon 6 (coding exon 6) of the TBPL2 gene. This alteration results from a T to C substitution at nucleotide position 958, causing the tyrosine (Y) at amino acid position 320 to be replaced by a histidine (H). 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