2-3546023-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002936.6(RNASEH1):​c.775-152G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 636,342 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 9 hom., cov: 32)
Exomes 𝑓: 0.00065 ( 2 hom. )

Consequence

RNASEH1
NM_002936.6 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.373
Variant links:
Genes affected
RNASEH1 (HGNC:18466): (ribonuclease H1) This gene encodes an endonuclease that specifically degrades the RNA of RNA-DNA hybrids and plays a key role in DNA replication and repair. Alternate in-frame start codon initiation results in the production of alternate isoforms that are directed to the mitochondria or to the nucleus. The production of the mitochondrial isoform is modulated by an upstream open reading frame (uORF). Mutations in this gene have been found in individuals with progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2. Alternative splicing results in additional coding and non-coding transcript variants. Pseudogenes of this gene have been defined on chromosomes 2 and 17. [provided by RefSeq, Jul 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BP6
Variant 2-3546023-C-T is Benign according to our data. Variant chr2-3546023-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1198046.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNASEH1NM_002936.6 linkuse as main transcriptc.775-152G>A intron_variant ENST00000315212.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNASEH1ENST00000315212.4 linkuse as main transcriptc.775-152G>A intron_variant 1 NM_002936.6 P1
RNASEH1ENST00000436842.5 linkuse as main transcriptc.*881-152G>A intron_variant, NMD_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.00377
AC:
574
AN:
152246
Hom.:
9
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0128
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00103
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00478
GnomAD4 exome
AF:
0.000653
AC:
316
AN:
483978
Hom.:
2
AF XY:
0.000613
AC XY:
158
AN XY:
257950
show subpopulations
Gnomad4 AFR exome
AF:
0.0132
Gnomad4 AMR exome
AF:
0.00127
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000287
Gnomad4 SAS exome
AF:
0.000653
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000846
Gnomad4 OTH exome
AF:
0.00131
GnomAD4 genome
AF:
0.00377
AC:
574
AN:
152364
Hom.:
9
Cov.:
32
AF XY:
0.00356
AC XY:
265
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.0127
Gnomad4 AMR
AF:
0.00118
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.00159
Hom.:
0
Bravo
AF:
0.00450
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxJan 28, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
2.0
DANN
Benign
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs115373330; hg19: chr2-3593613; API