2-46956923-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_020458.4(TTC7A):c.433G>T(p.Ala145Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A145T) has been classified as Uncertain significance.
Frequency
Consequence
NM_020458.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTC7A | NM_020458.4 | c.433G>T | p.Ala145Ser | missense_variant | 3/20 | ENST00000319190.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTC7A | ENST00000319190.11 | c.433G>T | p.Ala145Ser | missense_variant | 3/20 | 2 | NM_020458.4 | P1 | |
ENST00000607950.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251490Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135920
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727246
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Multiple gastrointestinal atresias Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 15, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 145 of the TTC7A protein (p.Ala145Ser). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with TTC7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1055896). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at