rs140528998
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_005149.3(TBX19):āc.627C>Gā(p.Tyr209Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,012 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 Pathogenic (ā ā ). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_005149.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX19 | NM_005149.3 | c.627C>G | p.Tyr209Ter | stop_gained | 4/8 | ENST00000367821.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX19 | ENST00000367821.8 | c.627C>G | p.Tyr209Ter | stop_gained | 4/8 | 1 | NM_005149.3 | P1 | |
TBX19 | ENST00000431969.5 | c.426C>G | p.Tyr142Ter | stop_gained | 3/6 | 5 | |||
TBX19 | ENST00000441464.1 | c.126C>G | p.Tyr42Ter | stop_gained | 1/5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251390Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135890
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461828Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727214
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74350
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 18, 2023 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge - |
Congenital isolated adrenocorticotropic hormone deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 01, 2017 | This nonsense variant is categorized as deleterious according to ACMG guidelines (PMID:18414213) and was found once in our laboratory homozygous in a 1-year-old male with global delays, hypotonia, dysmorphisms, structural brain abnormalities, congenital hypothyroidism, hyperinsulinismin the face of hypoglycemia, growth hormone deficiency, cortisol deficiency, anemia, jaundice, adrenal insufficiency. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at