rs376140250
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_032193.4(RNASEH2C):c.61T>C(p.Leu21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,594,188 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00059 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 25 hom. )
Consequence
RNASEH2C
NM_032193.4 synonymous
NM_032193.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.61
Genes affected
RNASEH2C (HGNC:24116): (ribonuclease H2 subunit C) This gene encodes a ribonuclease H subunit that can cleave ribonucleotides from RNA:DNA duplexes. Mutations in this gene cause Aicardi-Goutieres syndrome-3, a disease that causes severe neurologic dysfunction. A pseudogene for this gene has been identified on chromosome Y, near the sex determining region Y (SRY) gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 11-65720698-A-G is Benign according to our data. Variant chr11-65720698-A-G is described in ClinVar as [Benign]. Clinvar id is 305367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-65720698-A-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.61 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000592 (90/152092) while in subpopulation SAS AF= 0.0181 (87/4804). AF 95% confidence interval is 0.015. There are 1 homozygotes in gnomad4. There are 59 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNASEH2C | NM_032193.4 | c.61T>C | p.Leu21= | synonymous_variant | 1/4 | ENST00000308418.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNASEH2C | ENST00000308418.10 | c.61T>C | p.Leu21= | synonymous_variant | 1/4 | 1 | NM_032193.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000612 AC: 93AN: 151976Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00224 AC: 478AN: 213318Hom.: 7 AF XY: 0.00313 AC XY: 368AN XY: 117734
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GnomAD4 exome AF: 0.00113 AC: 1635AN: 1442096Hom.: 25 Cov.: 32 AF XY: 0.00166 AC XY: 1188AN XY: 716778
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GnomAD4 genome ? AF: 0.000592 AC: 90AN: 152092Hom.: 1 Cov.: 32 AF XY: 0.000793 AC XY: 59AN XY: 74388
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Aicardi-Goutieres syndrome 3 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at