rs146284515
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_020458.4(TTC7A):c.1189G>A(p.Val397Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000132 in 1,613,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. V397D) has been classified as Uncertain significance.
Frequency
Consequence
NM_020458.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTC7A | NM_020458.4 | c.1189G>A | p.Val397Ile | missense_variant | 9/20 | ENST00000319190.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTC7A | ENST00000319190.11 | c.1189G>A | p.Val397Ile | missense_variant | 9/20 | 2 | NM_020458.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 23AN: 152070Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000187 AC: 47AN: 251114Hom.: 0 AF XY: 0.000170 AC XY: 23AN XY: 135684
GnomAD4 exome AF: 0.000129 AC: 189AN: 1461558Hom.: 0 Cov.: 31 AF XY: 0.000140 AC XY: 102AN XY: 727036
GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74428
ClinVar
Submissions by phenotype
Multiple gastrointestinal atresias Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 21, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 397 of the TTC7A protein (p.Val397Ile). This variant is present in population databases (rs146284515, gnomAD 0.1%). 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: 572873). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TTC7A protein function with a negative predictive value of 80%. 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 31, 2022 | The c.1189G>A (p.V397I) alteration is located in exon 9 (coding exon 9) of the TTC7A gene. This alteration results from a G to A substitution at nucleotide position 1189, causing the valine (V) at amino acid position 397 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Aug 11, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at