chr19-12813343-C-T

Position:

chr19-12813343-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006397.3(RNASEH2A):c.777C>T(p.Ser259Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 1,614,052 control chromosomes in the GnomAD database, including 505 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 38 hom., cov: 32)

Exomes 𝑓: 0.022 ( 467 hom. )

Consequence

RNASEH2A
NM_006397.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.69

Variant links:

Genes affected

RNASEH2A (HGNC:18518): (ribonuclease H2 subunit A) The protein encoded by this gene is a component of the heterotrimeric type II ribonuclease H enzyme (RNAseH2). RNAseH2 is the major source of ribonuclease H activity in mammalian cells and endonucleolytically cleaves ribonucleotides. It is predicted to remove Okazaki fragment RNA primers during lagging strand DNA synthesis and to excise single ribonucleotides from DNA-DNA duplexes. Mutations in this gene cause Aicardi-Goutieres Syndrome (AGS), a an autosomal recessive neurological disorder characterized by progressive microcephaly and psychomotor retardation, intracranial calcifications, elevated levels of interferon-alpha and white blood cells in the cerebrospinal fluid.[provided by RefSeq, Aug 2009]

RNASEH2A links:

RNASEH2A (HGNC:):

RNASEH2A links:

THSD8 (HGNC:53785): (thrombospondin type 1 domain containing 8)

THSD8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 19-12813343-C-T is Benign according to our data. Variant chr19-12813343-C-T is described in ClinVar as [Benign]. Clinvar id is 328297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-12813343-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.69 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASEH2A	NM_006397.3 linkuse as main transcript	c.777C>T	p.Ser259Ser	synonymous_variant	8/8	ENST00000221486.6	NP_006388.2	O75792

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASEH2A	ENST00000221486.6 linkuse as main transcript	c.777C>T	p.Ser259Ser	synonymous_variant	8/8	1	NM_006397.3	ENSP00000221486.4		O75792

Frequencies

GnomAD3 genomes

AF:

0.0215

AC:

3275

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0452

Gnomad ASJ

AF:

0.0109

Gnomad EAS

AF:

0.0168

Gnomad SAS

AF:

0.0215

Gnomad FIN

AF:

0.0279

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0192

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.0293

AC:

7353

AN:

251156

Hom.:

178

AF XY:

0.0268

AC XY:

3646

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.0170

Gnomad AMR exome

AF:

0.0918

Gnomad ASJ exome

AF:

0.0114

Gnomad EAS exome

AF:

0.0175

Gnomad SAS exome

AF:

0.0227

Gnomad FIN exome

AF:

0.0267

Gnomad NFE exome

AF:

0.0181

Gnomad OTH exome

AF:

0.0225

GnomAD4 exome

AF:

0.0219

AC:

32002

AN:

1461844

Hom.:

467

Cov.:

AF XY:

0.0216

AC XY:

15741

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0180

Gnomad4 AMR exome

AF:

0.0877

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.0110

Gnomad4 SAS exome

AF:

0.0239

Gnomad4 FIN exome

AF:

0.0262

Gnomad4 NFE exome

AF:

0.0198

Gnomad4 OTH exome

AF:

0.0201

GnomAD4 genome

AF:

0.0215

AC:

3279

AN:

152208

Hom.:

Cov.:

AF XY:

0.0224

AC XY:

1668

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0174

Gnomad4 AMR

AF:

0.0450

Gnomad4 ASJ

AF:

0.0109

Gnomad4 EAS

AF:

0.0168

Gnomad4 SAS

AF:

0.0219

Gnomad4 FIN

AF:

0.0279

Gnomad4 NFE

AF:

0.0192

Gnomad4 OTH

AF:

0.0190

Alfa

AF:

0.0189

Hom.:

Bravo

AF:

0.0236

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.0170

EpiControl

AF:

0.0189

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 31, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Aicardi-Goutieres syndrome 4

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.12

DANN

Benign

0.39

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over