rs759925463
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_022489.4(INF2):āc.3412C>Gā(p.Leu1138Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,460,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. L1138L) has been classified as Uncertain significance.
Frequency
Consequence
NM_022489.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INF2 | NM_022489.4 | c.3412C>G | p.Leu1138Val | missense_variant | 21/23 | ENST00000392634.9 | |
INF2 | NM_001031714.4 | c.3412C>G | p.Leu1138Val | missense_variant | 21/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INF2 | ENST00000392634.9 | c.3412C>G | p.Leu1138Val | missense_variant | 21/23 | 5 | NM_022489.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 exomes AF: 0.0000404 AC: 10AN: 247806Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 134984
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1460348Hom.: 0 Cov.: 37 AF XY: 0.0000234 AC XY: 17AN XY: 726458
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Focal segmental glomerulosclerosis 5;C4302667:Charcot-Marie-Tooth disease dominant intermediate E Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2016 | In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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, but these predictions have not been confirmed by published functional studies. This variant is present in population databases (rs759925463, ExAC 0.02%) but has not been reported in the literature in individuals with a INF2-related disease. This sequence change replaces leucine with valine at codon 1138 of the INF2 protein (p.Leu1138Val). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and valine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at