chr19-12813460-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_006397.3(RNASEH2A):c.894C>A(p.Ser298Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,613,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_006397.3 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RNASEH2A | NM_006397.3 | c.894C>A | p.Ser298Arg | missense_variant | 8/8 | ENST00000221486.6 | NP_006388.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RNASEH2A | ENST00000221486.6 | c.894C>A | p.Ser298Arg | missense_variant | 8/8 | 1 | NM_006397.3 | ENSP00000221486 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000399 AC: 10AN: 250410Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135390
GnomAD4 exome AF: 0.000129 AC: 189AN: 1461152Hom.: 0 Cov.: 32 AF XY: 0.000143 AC XY: 104AN XY: 726892
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74296
ClinVar
Submissions by phenotype
Aicardi-Goutieres syndrome 4 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 12, 2022 | This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 298 of the RNASEH2A protein (p.Ser298Arg). This variant is present in population databases (rs760066036, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with RNASEH2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 448168). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 06, 2017 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2022 | The c.894C>A (p.S298R) alteration is located in exon 8 (coding exon 8) of the RNASEH2A gene. This alteration results from a C to A substitution at nucleotide position 894, causing the serine (S) at amino acid position 298 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at