rs150370681
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_020800.3(IFT80):c.1883G>A(p.Arg628Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000433 in 1,613,656 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 (★★).
Frequency
Consequence
NM_020800.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IFT80 | NM_020800.3 | c.1883G>A | p.Arg628Gln | missense_variant | 17/20 | ENST00000326448.12 | |
TRIM59-IFT80 | NR_148401.1 | n.2591G>A | non_coding_transcript_exon_variant | 15/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFT80 | ENST00000326448.12 | c.1883G>A | p.Arg628Gln | missense_variant | 17/20 | 1 | NM_020800.3 | P1 | |
IFT80 | ENST00000483465.5 | c.1472G>A | p.Arg491Gln | missense_variant | 16/19 | 1 | |||
IFT80 | ENST00000496589.5 | c.1472G>A | p.Arg491Gln | missense_variant | 18/21 | 2 | |||
IFT80 | ENST00000487943.5 | n.3102G>A | non_coding_transcript_exon_variant | 17/20 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000388 AC: 59AN: 152120Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000355 AC: 89AN: 250436Hom.: 0 AF XY: 0.000347 AC XY: 47AN XY: 135358
GnomAD4 exome AF: 0.000438 AC: 640AN: 1461418Hom.: 0 Cov.: 30 AF XY: 0.000447 AC XY: 325AN XY: 726998
GnomAD4 genome ? AF: 0.000388 AC: 59AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74432
ClinVar
Submissions by phenotype
Asphyxiating thoracic dystrophy 2 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 29, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 06, 2015 | - - |
Jeune thoracic dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 628 of the IFT80 protein (p.Arg628Gln). This variant is present in population databases (rs150370681, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with IFT80-related conditions. ClinVar contains an entry for this variant (Variation ID: 194779). 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 IFT80 protein function. 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