rs786205698
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_020458.4(TTC7A):c.1576C>T(p.Gln526Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,086 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 (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_020458.4 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTC7A | NM_020458.4 | c.1576C>T | p.Gln526Ter | stop_gained | 14/20 | ENST00000319190.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTC7A | ENST00000319190.11 | c.1576C>T | p.Gln526Ter | stop_gained | 14/20 | 2 | NM_020458.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000411 AC: 1AN: 243490Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 131690
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1454086Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 722818
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Gastrointestinal defects and immunodeficiency syndrome 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2014 | - - |
Multiple gastrointestinal atresias Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 24, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 190393). This premature translational stop signal has been observed in individual(s) with very early onset inflammatory bowel disease (PMID: 24417819). This variant is present in population databases (rs786205698, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Gln526*) in the TTC7A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TTC7A are known to be pathogenic (PMID: 23830146, 24292712). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at