12-110127405-A-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_014055.4(IFT81):āc.25A>Gā(p.Met9Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000219 in 1,595,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_014055.4 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 |
---|---|---|---|---|---|---|---|
IFT81 | NM_014055.4 | c.25A>G | p.Met9Val | missense_variant | 2/19 | ENST00000242591.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFT81 | ENST00000242591.10 | c.25A>G | p.Met9Val | missense_variant | 2/19 | 1 | NM_014055.4 | P1 | |
IFT81 | ENST00000552912.5 | c.25A>G | p.Met9Val | missense_variant | 2/19 | 1 | P1 | ||
IFT81 | ENST00000361948.8 | c.25A>G | p.Met9Val | missense_variant | 2/12 | 1 | |||
IFT81 | ENST00000546374.5 | c.25A>G | p.Met9Val | missense_variant | 2/10 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152200Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000351 AC: 8AN: 227754Hom.: 0 AF XY: 0.0000244 AC XY: 3AN XY: 123178
GnomAD4 exome AF: 0.0000111 AC: 16AN: 1443018Hom.: 0 Cov.: 30 AF XY: 0.0000112 AC XY: 8AN XY: 717008
GnomAD4 genome AF: 0.000125 AC: 19AN: 152200Hom.: 0 Cov.: 31 AF XY: 0.000134 AC XY: 10AN XY: 74354
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 17, 2023 | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 9 of the IFT81 protein (p.Met9Val). This variant is present in population databases (rs375743897, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with IFT81-related conditions. ClinVar contains an entry for this variant (Variation ID: 1039058). 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 IFT81 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