rs569884568
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_020070.4(IGLL1):c.197G>T(p.Arg66Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R66G) has been classified as Uncertain significance.
Frequency
Consequence
NM_020070.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGLL1 | NM_020070.4 | c.197G>T | p.Arg66Leu | missense_variant | 1/3 | ENST00000330377.3 | |
IGLL1 | NM_001369906.1 | c.197G>T | p.Arg66Leu | missense_variant | 1/3 | ||
IGLL1 | NM_152855.3 | c.197G>T | p.Arg66Leu | missense_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGLL1 | ENST00000330377.3 | c.197G>T | p.Arg66Leu | missense_variant | 1/3 | 1 | NM_020070.4 | P1 | |
IGLL1 | ENST00000249053.3 | c.197G>T | p.Arg66Leu | missense_variant | 1/2 | 1 | |||
IGLL1 | ENST00000438703.1 | c.197G>T | p.Arg66Leu | missense_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1428904Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 708984
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Agammaglobulinemia 2, autosomal recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 15, 2019 | 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 and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with IGLL1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with leucine at codon 66 of the IGLL1 protein (p.Arg66Leu). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at