Variant rs141875736 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 3P and 16B. PM1PM4_SupportingBP6_Very_StrongBA1

The NM_032193.4(RNASEH2C):c.268_270delAAG(p.Lys90del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,614,274 control chromosomes in the GnomAD database, including 354 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 46 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 308 hom. )

Consequence

RNASEH2C
NM_032193.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.855

Variant links:

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]

RNASEH2C links:

RNASEH2C (HGNC:):

RNASEH2C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PM1

In a chain Ribonuclease H2 subunit C (size 163) in uniprot entity RNH2C_HUMAN there are 16 pathogenic changes around while only 2 benign (89%) in NM_032193.4

PM4

Nonframeshift variant in NON repetitive region in NM_032193.4. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 11-65720319-CCTT-C is Benign according to our data. Variant chr11-65720319-CCTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 305363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-65720319-CCTT-C is described in Lovd as [Benign]. Variant chr11-65720319-CCTT-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASEH2C	NM_032193.4 linkuse as main transcript	c.268_270delAAG	p.Lys90del	conservative_inframe_deletion	2/4	ENST00000308418.10	NP_115569.2	Q8TDP1A0A024R5B3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASEH2C	ENST00000308418.10 linkuse as main transcript	c.268_270delAAG	p.Lys90del	conservative_inframe_deletion	2/4	1	NM_032193.4	ENSP00000308193.5		Q8TDP1

Frequencies

GnomAD3 genomes

AF:

0.00512

AC:

779

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.00475

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.0108

AC:

2727

AN:

251488

Hom.:

206

AF XY:

0.00983

AC XY:

1336

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.138

Gnomad SAS exome

AF:

0.00294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000378

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00392

AC:

5733

AN:

1461890

Hom.:

308

AF XY:

0.00385

AC XY:

2797

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.000715

Gnomad4 ASJ exome

AF:

0.00103

Gnomad4 EAS exome

AF:

0.117

Gnomad4 SAS exome

AF:

0.00351

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000353

Gnomad4 OTH exome

AF:

0.00477

GnomAD4 genome

AF:

0.00510

AC:

777

AN:

152384

Hom.:

Cov.:

AF XY:

0.00609

AC XY:

454

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.129

Gnomad4 SAS

AF:

0.00496

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00143

Hom.:

Bravo

AF:

0.00609

Asia WGS

AF:

0.0410

AC:

142

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Apr 22, 2022	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 15, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Aicardi Goutieres syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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