rs200705429
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_015631.6(TCTN3):c.1271T>G(p.Val424Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_015631.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TCTN3 | ENST00000371217.10 | c.1271T>G | p.Val424Gly | missense_variant | Exon 11 of 14 | 1 | NM_015631.6 | ENSP00000360261.5 | ||
TCTN3 | ENST00000265993.13 | c.1325T>G | p.Val442Gly | missense_variant | Exon 11 of 14 | 1 | ENSP00000265993.9 | |||
TCTN3 | ENST00000430368.6 | c.827T>G | p.Val276Gly | missense_variant | Exon 7 of 10 | 2 | ENSP00000387567.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152110Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251396Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135854
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461770Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727180
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74312
ClinVar
Submissions by phenotype
Orofacial-digital syndrome IV;C3553758:Joubert syndrome 18 Uncertain:2
- -
This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 424 of the TCTN3 protein (p.Val424Gly). This variant is present in population databases (rs200705429, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with TCTN3-related conditions. ClinVar contains an entry for this variant (Variation ID: 473271). 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. -
Inborn genetic diseases Uncertain:1
The c.1271T>G (p.V424G) alteration is located in exon 11 (coding exon 11) of the TCTN3 gene. This alteration results from a T to G substitution at nucleotide position 1271, causing the valine (V) at amino acid position 424 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at