chr16-1557968-T-A
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_014714.4(IFT140):c.2366A>T(p.Asp789Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D789D) has been classified as Likely benign.
Frequency
Consequence
NM_014714.4 missense
Scores
Clinical Significance
Conservation
Publications
- autosomal dominant polycystic kidney diseaseInheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
- IFT140-related recessive ciliopathyInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Illumina
- short-rib thoracic dysplasia 9 with or without polydactylyInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
- retinitis pigmentosa 80Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- Leber congenital amaurosisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- retinitis pigmentosaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Jeune syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Saldino-Mainzer syndrome Uncertain:1
This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 789 of the IFT140 protein (p.Asp789Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with IFT140-related conditions. ClinVar contains an entry for this variant (Variation ID: 465315). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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