chr11-298613-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001025295.3(IFITM5):c.287C>T(p.Pro96Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,613,308 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 (★★). Synonymous variant affecting the same amino acid position (i.e. P96P) has been classified as Likely benign.
Frequency
Consequence
NM_001025295.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IFITM5 | NM_001025295.3 | c.287C>T | p.Pro96Leu | missense_variant | 2/2 | ENST00000382614.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFITM5 | ENST00000382614.2 | c.287C>T | p.Pro96Leu | missense_variant | 2/2 | 1 | NM_001025295.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152240Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000640 AC: 16AN: 249922Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135510
GnomAD4 exome AF: 0.000118 AC: 173AN: 1461068Hom.: 0 Cov.: 31 AF XY: 0.000117 AC XY: 85AN XY: 726840
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74366
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 19, 2022 | The c.287C>T (p.P96L) alteration is located in exon 2 (coding exon 2) of the IFITM5 gene. This alteration results from a C to T substitution at nucleotide position 287, causing the proline (P) at amino acid position 96 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 12, 2023 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 2192954). This variant has not been reported in the literature in individuals affected with IFITM5-related conditions. This variant is present in population databases (rs371737593, gnomAD 0.01%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 96 of the IFITM5 protein (p.Pro96Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at