chr13-50910101-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_024570.4(RNASEH2B):āc.25G>Cā(p.Asp9His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,310,940 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D9N) 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.25G>C | p.Asp9His | missense_variant | 1/11 | ENST00000336617.8 | |
RNASEH2B-AS1 | NR_046552.1 | n.230+382C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNASEH2B | ENST00000336617.8 | c.25G>C | p.Asp9His | missense_variant | 1/11 | 1 | NM_024570.4 | P3 | |
RNASEH2B-AS1 | ENST00000596992.5 | n.112+382C>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000153 AC: 2AN: 1310940Hom.: 0 Cov.: 31 AF XY: 0.00000310 AC XY: 2AN XY: 644836
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Aicardi-Goutieres syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 02, 2021 | This sequence change replaces aspartic acid with histidine at codon 9 of the RNASEH2B protein (p.Asp9His). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with RNASEH2B-related conditions. 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: "Not Available"; 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at