chr13-50910116-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_024570.4(RNASEH2B):c.40C>T(p.Arg14Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,458,770 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. R14Q) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNASEH2B | NM_024570.4 | c.40C>T | p.Arg14Trp | missense_variant | 1/11 | ENST00000336617.8 | |
RNASEH2B-AS1 | NR_046552.1 | n.230+367G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNASEH2B | ENST00000336617.8 | c.40C>T | p.Arg14Trp | missense_variant | 1/11 | 1 | NM_024570.4 | P3 | |
RNASEH2B-AS1 | ENST00000596992.5 | n.112+367G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 151852Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000583 AC: 4AN: 68664Hom.: 0 AF XY: 0.0000506 AC XY: 2AN XY: 39500
GnomAD4 exome AF: 0.000119 AC: 155AN: 1306918Hom.: 0 Cov.: 31 AF XY: 0.000104 AC XY: 67AN XY: 642356
GnomAD4 genome AF: 0.0000395 AC: 6AN: 151852Hom.: 0 Cov.: 32 AF XY: 0.0000405 AC XY: 3AN XY: 74160
ClinVar
Submissions by phenotype
Aicardi-Goutieres syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 14 of the RNASEH2B protein (p.Arg14Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with RNASEH2B-related conditions. ClinVar contains an entry for this variant (Variation ID: 540250). 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 RNASEH2B 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at