rs918089359
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2PM5PP3_StrongPP5_Moderate
The NM_022489.4(INF2):c.218G>T(p.Gly73Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G73S) has been classified as Pathogenic.
Frequency
Consequence
NM_022489.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INF2 | NM_022489.4 | c.218G>T | p.Gly73Val | missense_variant | 2/23 | ENST00000392634.9 | |
INF2 | NM_001031714.4 | c.218G>T | p.Gly73Val | missense_variant | 2/22 | ||
INF2 | NM_032714.3 | c.218G>T | p.Gly73Val | missense_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INF2 | ENST00000392634.9 | c.218G>T | p.Gly73Val | missense_variant | 2/23 | 5 | NM_022489.4 | P4 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1455218Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 723904
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Focal segmental glomerulosclerosis 5;C4302667:Charcot-Marie-Tooth disease dominant intermediate E Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 07, 2020 | For these reasons, this variant has been classified as Pathogenic. 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"). This variant has been observed in individual(s) with clinical features of INF2-related conditions (PMID: 31937884, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 472842). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 73 of the INF2 protein (p.Gly73Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at