rs587776971
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The ENST00000319190.11(TTC7A):c.1000_1001+2delAAGT(p.Asn334SerfsTer28) variant causes a frameshift, splice donor, splice region, intron change. The variant allele was found at a frequency of 0.0000266 in 1,613,646 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000319190.11 frameshift, splice_donor, splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152134Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250650Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135568
GnomAD4 exome AF: 0.0000260 AC: 38AN: 1461512Hom.: 0 AF XY: 0.0000275 AC XY: 20AN XY: 727042
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74320
ClinVar
Submissions by phenotype
Gastrointestinal defects and immunodeficiency syndrome 1 Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 26, 2024 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2013 | - - |
Pathogenic, criteria provided, single submitter | research | Aleixo Muise Laboratory, Hospital For Sick Children | Jul 05, 2024 | PS1;PM2;PM3;PP3;PP4 - |
TTC7A-related disorder Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 04, 2024 | The TTC7A c.1001+3_1001+6delAAGT variant is predicted to result in an intronic deletion. This variant was reported in the homozygous and compound heterozygous state with a second pathogenic variant in multiple individuals with multiple intestinal atresia (also described as c.53344_53347delAAGT or c.1000delAAGT; Samuels et al. 2013. PubMed ID: 23423984; Chen et al. 2013. PubMed ID: 23830146; Table E1, Stray-Pedersen et al. 2016. PubMed ID: 27577878; Mandiá et al. 2018. PubMed ID: 29879038). This variant is reported in 0.0079% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at