chr6-166929652-C-T

Position:

chr6-166929652-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000508775.6(RNASET2):c.707G>A(p.Arg236Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000846 in 1,614,072 control chromosomes in the GnomAD database, including 4 homozygotes. 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R236W) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00099 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00083 ( 3 hom. )

Consequence

RNASET2
ENST00000508775.6 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.463

Variant links:

Genes affected

RNASET2 (HGNC:21686): (ribonuclease T2) This ribonuclease gene is a novel member of the Rh/T2/S-glycoprotein class of extracellular ribonucleases. It is a single copy gene that maps to 6q27, a region associated with human malignancies and chromosomal rearrangement. [provided by RefSeq, Jul 2008]

RNASET2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039610565).

BP6

Variant 6-166929652-C-T is Benign according to our data. Variant chr6-166929652-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 716206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-166929652-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000992 (151/152214) while in subpopulation EAS AF= 0.00444 (23/5180). AF 95% confidence interval is 0.00303. There are 1 homozygotes in gnomad4. There are 87 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASET2	NM_003730.6 linkuse as main transcript	c.707G>A	p.Arg236Gln	missense_variant	9/9	ENST00000508775.6	NP_003721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASET2	ENST00000508775.6 linkuse as main transcript	c.707G>A	p.Arg236Gln	missense_variant	9/9	1	NM_003730.6	ENSP00000426455	P1	O00584-1

Frequencies

GnomAD3 genomes

AF:

0.000993

AC:

151

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00443

Gnomad SAS

AF:

0.00291

Gnomad FIN

AF:

0.00736

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00156

AC:

393

AN:

251356

Hom.:

AF XY:

0.00169

AC XY:

230

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00370

Gnomad SAS exome

AF:

0.00173

Gnomad FIN exome

AF:

0.00776

Gnomad NFE exome

AF:

0.000545

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.000831

AC:

1215

AN:

1461858

Hom.:

Cov.:

AF XY:

0.000866

AC XY:

630

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000693

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00345

Gnomad4 SAS exome

AF:

0.00195

Gnomad4 FIN exome

AF:

0.00876

Gnomad4 NFE exome

AF:

0.000311

Gnomad4 OTH exome

AF:

0.000993

GnomAD4 genome

AF:

0.000992

AC:

151

AN:

152214

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00444

Gnomad4 SAS

AF:

0.00291

Gnomad4 FIN

AF:

0.00736

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000509

Hom.:

Bravo

AF:

0.000427

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00156

AC:

189

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cystic leukoencephalopathy without megalencephaly

Benign:1

Likely benign, 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 02, 2024

- -

RNASET2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 07, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.4

DANN

Benign

0.81

DEOGEN2

Benign

0.0027

.;T;T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.55

T;.;T;T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.0040

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.29

.;N;.;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

0.57

N;N;.;N;N

REVEL

Benign

0.041

Sift

Benign

0.59

T;T;.;T;T

Sift4G

Benign

0.58

T;T;T;T;.

Polyphen

0.071

.;B;.;B;.

Vest4

0.061

MVP

0.23

MPC

0.27

ClinPred

0.0073

GERP RS

-3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.083

gMVP

0.22

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