rs201926069
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_000538.4(RFXAP):c.456G>C(p.Gln152His) variant causes a missense change. The variant allele was found at a frequency of 0.0000457 in 1,597,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. Q152R) has been classified as Uncertain significance.
Frequency
Consequence
NM_000538.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RFXAP | NM_000538.4 | c.456G>C | p.Gln152His | missense_variant | 1/3 | ENST00000255476.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RFXAP | ENST00000255476.3 | c.456G>C | p.Gln152His | missense_variant | 1/3 | 1 | NM_000538.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000223 AC: 34AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000495 AC: 11AN: 222160Hom.: 0 AF XY: 0.0000501 AC XY: 6AN XY: 119866
GnomAD4 exome AF: 0.0000270 AC: 39AN: 1445426Hom.: 0 Cov.: 32 AF XY: 0.0000251 AC XY: 18AN XY: 717132
GnomAD4 genome ? AF: 0.000223 AC: 34AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74368
ClinVar
Submissions by phenotype
MHC class II deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 152 of the RFXAP protein (p.Gln152His). This variant is present in population databases (rs201926069, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with RFXAP-related conditions. ClinVar contains an entry for this variant (Variation ID: 573717). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RFXAP 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 specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2021 | The c.456G>C (p.Q152H) alteration is located in exon 1 (coding exon 1) of the RFXAP gene. This alteration results from a G to C substitution at nucleotide position 456, causing the glutamine (Q) at amino acid position 152 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at