rs149253747
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_000246.4(CIITA):c.286G>A(p.Ala96Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000525 in 1,613,970 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000246.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CIITA | NM_000246.4 | c.286G>A | p.Ala96Thr | missense_variant | 3/20 | ENST00000324288.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CIITA | ENST00000324288.14 | c.286G>A | p.Ala96Thr | missense_variant | 3/20 | 1 | NM_000246.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000467 AC: 71AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000469 AC: 118AN: 251444Hom.: 0 AF XY: 0.000471 AC XY: 64AN XY: 135888
GnomAD4 exome AF: 0.000532 AC: 777AN: 1461824Hom.: 2 Cov.: 32 AF XY: 0.000542 AC XY: 394AN XY: 727214
GnomAD4 genome ? AF: 0.000467 AC: 71AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.000444 AC XY: 33AN XY: 74310
ClinVar
Submissions by phenotype
MHC class II deficiency Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 10, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 19, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 96 of the CIITA protein (p.Ala96Thr). This variant is present in population databases (rs149253747, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. 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: 528783). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 02, 2024 | The c.286G>A (p.A96T) alteration is located in exon 3 (coding exon 3) of the CIITA gene. This alteration results from a G to A substitution at nucleotide position 286, causing the alanine (A) at amino acid position 96 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Rheumatoid arthritis;C2931418:MHC class II deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | CIITA NM_000246.3 exon 3 p.Ala96Thr (c.286G>A):This variant has not been reported in the literature but is present in 0.08% (60/68036) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/16-10895755-G-A?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:528783). Evolutionary conservation for this variant is unclear; computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at