chr13-50930707-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_024570.4(RNASEH2B):c.269C>T(p.Pro90Leu) 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 1,613,714 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. P90R) has been classified as Uncertain significance.
Frequency
Consequence
NM_024570.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNASEH2B | NM_024570.4 | c.269C>T | p.Pro90Leu | missense_variant | 4/11 | ENST00000336617.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNASEH2B | ENST00000336617.8 | c.269C>T | p.Pro90Leu | missense_variant | 4/11 | 1 | NM_024570.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152222Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000135 AC: 34AN: 251404Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135864
GnomAD4 exome AF: 0.0000239 AC: 35AN: 1461492Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 727076
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74360
ClinVar
Submissions by phenotype
Aicardi-Goutieres syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 90 of the RNASEH2B protein (p.Pro90Leu). This variant is present in population databases (rs770203126, gnomAD 0.2%). This missense change has been observed in individual(s) with Aicardi-Goutières syndrome (PMID: 33482855). ClinVar contains an entry for this variant (Variation ID: 540249). 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 disruptive. 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