chr13-50910079-G-A
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_024570.4(RNASEH2B):c.3G>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000763 in 1,311,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.6e-7 ( 0 hom. )
Consequence
RNASEH2B
NM_024570.4 start_lost
NM_024570.4 start_lost
Scores
6
4
6
Clinical Significance
Conservation
PhyloP100: 2.31
Genes affected
RNASEH2B (HGNC:25671): (ribonuclease H2 subunit B) RNase H2 is composed of a single catalytic subunit (A) and two non-catalytic subunits (B and C) and specifically degrades the RNA of RNA:DNA hybrids. The protein encoded by this gene is the non-catalytic B subunit of RNase H2, which is thought to play a role in DNA replication. Multiple transcript variants encoding different isoforms have been found for this gene. Defects in this gene are a cause of Aicardi-Goutieres syndrome type 2 (AGS2). [provided by RefSeq, Nov 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Start lost variant, no new inframe start found.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 13-50910079-G-A is Pathogenic according to our data. Variant chr13-50910079-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 280090.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RNASEH2B | NM_024570.4 | c.3G>A | p.Met1? | start_lost | 1/11 | ENST00000336617.8 | NP_078846.2 | |
RNASEH2B-AS1 | NR_046552.1 | n.230+404C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RNASEH2B | ENST00000336617.8 | c.3G>A | p.Met1? | start_lost | 1/11 | 1 | NM_024570.4 | ENSP00000337623 | P3 | |
RNASEH2B-AS1 | ENST00000596992.5 | n.112+404C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 7.63e-7 AC: 1AN: 1311152Hom.: 0 Cov.: 31 AF XY: 0.00000155 AC XY: 1AN XY: 645094
GnomAD4 exome
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1
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1311152
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31
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1
AN XY:
645094
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 16, 2016 | The c.3 G>A pathogenic variant in the RNASEH2B gene has been reported previously in the presence of another RNASEH2B pathogenic variant, in two related individuals with Aicardi-Goutieres syndrome (Rice et al., 2013). Data from control individuals was not sufficient to assess whether c.3 G>A may be a common benign variant in the general population. As this pathogenic variant changes the translation initiator Methionine codon, the resultant protein is described as p.Met1?, using a question mark to signify that it is not known if the loss of Met1 means that all protein translation is completely prevented or if an abnormal protein is produced using an alternate Methionine. Therefore, we interpret c.3 G>A as a pathogenic variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.;.;.;.;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PROVEAN
Benign
N;N;.;.;.;.;.;.;.;.;.;.
REVEL
Uncertain
Sift
Pathogenic
D;D;.;.;.;.;.;.;.;.;.;.
Sift4G
Pathogenic
D;D;.;.;.;.;.;.;.;.;.;.
Polyphen
B;.;.;.;.;.;.;.;.;.;.;.
Vest4
MutPred
Gain of catalytic residue at D6 (P = 0);Gain of catalytic residue at D6 (P = 0);Gain of catalytic residue at D6 (P = 0);Gain of catalytic residue at D6 (P = 0);Gain of catalytic residue at D6 (P = 0);Gain of catalytic residue at D6 (P = 0);Gain of catalytic residue at D6 (P = 0);Gain of catalytic residue at D6 (P = 0);Gain of catalytic residue at D6 (P = 0);Gain of catalytic residue at D6 (P = 0);Gain of catalytic residue at D6 (P = 0);Gain of catalytic residue at D6 (P = 0);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at