rs199476070
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000246.4(CIITA):c.1684G>A(p.Ala562Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,494 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 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. A562D) has been classified as Uncertain significance.
Frequency
Consequence
NM_000246.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CIITA | NM_000246.4 | c.1684G>A | p.Ala562Thr | missense_variant | 11/20 | ENST00000324288.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CIITA | ENST00000324288.14 | c.1684G>A | p.Ala562Thr | missense_variant | 11/20 | 1 | NM_000246.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152042Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000485 AC: 12AN: 247490Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 134990
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461332Hom.: 1 Cov.: 67 AF XY: 0.0000179 AC XY: 13AN XY: 726988
GnomAD4 genome ? AF: 0.0000789 AC: 12AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74394
ClinVar
Submissions by phenotype
MHC class II deficiency Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 06, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 08, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 562 of the CIITA protein (p.Ala562Thr). This variant is present in population databases (rs199476070, gnomAD 0.04%). 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: 102994). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine 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. - |
not provided Other:1
not provided, no classification provided | literature only | Human Evolutionary Genetics, Institut Pasteur | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at