6-166929653-G-A

Position:

chr6-166929653-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003730.6(RNASET2):c.706C>T(p.Arg236Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 1,613,952 control chromosomes in the GnomAD database, including 4,376 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R236Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.079 ( 518 hom., cov: 33)

Exomes 𝑓: 0.071 ( 3858 hom. )

Consequence

RNASET2
NM_003730.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.601

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:

ENSG00000249141 (HGNC:):

ENSG00000249141 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=0.001725316).

BP6

Variant 6-166929653-G-A is Benign according to our data. Variant chr6-166929653-G-A is described in ClinVar as [Benign]. Clinvar id is 356027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-166929653-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASET2	NM_003730.6 link	c.706C>T	p.Arg236Trp	missense_variant	9/9	ENST00000508775.6	NP_003721.2	O00584-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASET2	ENST00000508775.6 link	c.706C>T	p.Arg236Trp	missense_variant	9/9	1	NM_003730.6	ENSP00000426455.2		O00584-1
ENSG00000249141	ENST00000507747.1 link	c.432+4438C>T		intron_variant		5		ENSP00000426906.1		H0YAE9

Frequencies

GnomAD3 genomes

AF:

0.0793

AC:

12046

AN:

151986

Hom.:

517

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.0418

Gnomad AMR

AF:

0.0663

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.0597

Gnomad SAS

AF:

0.0558

Gnomad FIN

AF:

0.0555

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0694

Gnomad OTH

AF:

0.0772

GnomAD3 exomes

AF:

0.0689

AC:

17325

AN:

251354

Hom.:

664

AF XY:

0.0693

AC XY:

9415

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.0478

Gnomad ASJ exome

AF:

0.132

Gnomad EAS exome

AF:

0.0633

Gnomad SAS exome

AF:

0.0577

Gnomad FIN exome

AF:

0.0582

Gnomad NFE exome

AF:

0.0706

Gnomad OTH exome

AF:

0.0738

GnomAD4 exome

AF:

0.0709

AC:

103612

AN:

1461848

Hom.:

3858

Cov.:

AF XY:

0.0709

AC XY:

51578

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.0505

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.0468

Gnomad4 SAS exome

AF:

0.0601

Gnomad4 FIN exome

AF:

0.0593

Gnomad4 NFE exome

AF:

0.0712

Gnomad4 OTH exome

AF:

0.0753

GnomAD4 genome

AF:

0.0793

AC:

12061

AN:

152104

Hom.:

518

Cov.:

AF XY:

0.0777

AC XY:

5776

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.108

Gnomad4 AMR

AF:

0.0662

Gnomad4 ASJ

AF:

0.129

Gnomad4 EAS

AF:

0.0596

Gnomad4 SAS

AF:

0.0559

Gnomad4 FIN

AF:

0.0555

Gnomad4 NFE

AF:

0.0694

Gnomad4 OTH

AF:

0.0769

Alfa

AF:

0.0749

Hom.:

415

Bravo

AF:

0.0815

TwinsUK

AF:

0.0728

AC:

270

ALSPAC

AF:

0.0747

AC:

288

ESP6500AA

AF:

0.109

AC:

482

ESP6500EA

AF:

0.0767

AC:

660

ExAC

AF:

0.0695

AC:

8433

Asia WGS

AF:

0.0680

AC:

238

AN:

3478

EpiCase

AF:

0.0779

EpiControl

AF:

0.0730

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cystic leukoencephalopathy without megalencephaly

Benign:3

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	May 31, 2017	- -
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.010

.;T;T;T;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.70

T;.;T;T;T

MetaRNN

Benign

0.0017

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L;.;L;.

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.4

N;N;.;N;N

REVEL

Benign

0.18

Sift

Uncertain

0.018

D;D;.;D;D

Sift4G

Uncertain

0.018

D;D;D;D;.

Polyphen

0.99

.;D;.;D;.

Vest4

0.12

MPC

0.56

ClinPred

0.017

GERP RS

0.021

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.44

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