rs376916824
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000246.4(CIITA):c.1643G>A(p.Arg548Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000118 in 1,612,100 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R548L) has been classified as Uncertain significance.
Frequency
Consequence
NM_000246.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CIITA | NM_000246.4 | c.1643G>A | p.Arg548Gln | missense_variant | 11/20 | ENST00000324288.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CIITA | ENST00000324288.14 | c.1643G>A | p.Arg548Gln | missense_variant | 11/20 | 1 | NM_000246.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000659 AC: 10AN: 151842Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000106 AC: 26AN: 244700Hom.: 0 AF XY: 0.0000971 AC XY: 13AN XY: 133836
GnomAD4 exome AF: 0.000123 AC: 180AN: 1460258Hom.: 0 Cov.: 67 AF XY: 0.000116 AC XY: 84AN XY: 726458
GnomAD4 genome ? AF: 0.0000659 AC: 10AN: 151842Hom.: 0 Cov.: 32 AF XY: 0.0000944 AC XY: 7AN XY: 74164
ClinVar
Submissions by phenotype
MHC class II deficiency Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 548 of the CIITA protein (p.Arg548Gln). This variant is present in population databases (rs376916824, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CIITA-related conditions. ClinVar contains an entry for this variant (Variation ID: 663834). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C35". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at