rs376455886
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001008537.3(NEXMIF):c.911G>T(p.Gly304Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000414 in 1,208,594 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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. G304S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001008537.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEXMIF | NM_001008537.3 | c.911G>T | p.Gly304Val | missense_variant | 3/4 | ENST00000055682.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEXMIF | ENST00000055682.12 | c.911G>T | p.Gly304Val | missense_variant | 3/4 | 1 | NM_001008537.3 | P1 | |
NEXMIF | ENST00000616200.2 | c.911G>T | p.Gly304Val | missense_variant | 3/5 | 1 | P1 | ||
NEXMIF | ENST00000642681.2 | c.911G>T | p.Gly304Val | missense_variant | 3/3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000179 AC: 2AN: 111953Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 34123
GnomAD3 exomes AF: 0.00000546 AC: 1AN: 183034Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67628
GnomAD4 exome AF: 0.00000274 AC: 3AN: 1096641Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1AN XY: 362045
GnomAD4 genome ? AF: 0.0000179 AC: 2AN: 111953Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 34123
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 304 of the KIAA2022 protein (p.Gly304Val). This variant is present in population databases (rs376455886, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with KIAA2022-related conditions. ClinVar contains an entry for this variant (Variation ID: 574203). 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 C15"). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 26, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at