19-19201702-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003721.4(RFXANK):c.766C>T(p.Pro256Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_003721.4 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RFXANK | NM_003721.4 | c.766C>T | p.Pro256Ser | missense_variant | Exon 10 of 10 | ENST00000303088.9 | NP_003712.1 | |
NR2C2AP | NM_176880.6 | c.*223G>A | 3_prime_UTR_variant | Exon 5 of 5 | ENST00000331552.12 | NP_795361.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RFXANK | ENST00000303088.9 | c.766C>T | p.Pro256Ser | missense_variant | Exon 10 of 10 | 1 | NM_003721.4 | ENSP00000305071.2 | ||
NR2C2AP | ENST00000331552 | c.*223G>A | 3_prime_UTR_variant | Exon 5 of 5 | 1 | NM_176880.6 | ENSP00000332823.6 | |||
NR2C2AP | ENST00000420605.7 | c.415-139G>A | intron_variant | Intron 5 of 5 | 2 | ENSP00000402756.1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152210Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000758 AC: 19AN: 250608Hom.: 0 AF XY: 0.0000885 AC XY: 12AN XY: 135542
GnomAD4 exome AF: 0.0000595 AC: 87AN: 1461764Hom.: 0 Cov.: 31 AF XY: 0.0000495 AC XY: 36AN XY: 727192
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74354
ClinVar
Submissions by phenotype
MHC class II deficiency Uncertain:1
This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 256 of the RFXANK protein (p.Pro256Ser). This variant is present in population databases (rs759707164, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RFXANK-related conditions. ClinVar contains an entry for this variant (Variation ID: 651963). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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