Variant 6-166929662-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_003730.6(RNASET2):c.697G>A(p.Ala233Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000978 in 1,614,092 control chromosomes in the GnomAD database, including 14 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 (★).

Frequency

Genomes: 𝑓 0.0056 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00050 ( 5 hom. )

Consequence

RNASET2
NM_003730.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.08

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040089786).

BP6

Variant 6-166929662-C-T is Benign according to our data. Variant chr6-166929662-C-T is described in ClinVar as [Benign]. Clinvar id is 776184.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-166929662-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00558 (850/152244) while in subpopulation AFR AF= 0.0195 (812/41544). AF 95% confidence interval is 0.0184. There are 9 homozygotes in gnomad4. There are 403 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASET2	NM_003730.6 link	c.697G>A	p.Ala233Thr	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.697G>A	p.Ala233Thr	missense_variant	9/9	1	NM_003730.6	ENSP00000426455.2		O00584-1
ENSG00000249141	ENST00000507747.1 link	c.432+4429G>A		intron_variant		5		ENSP00000426906.1		H0YAE9

Frequencies

GnomAD3 genomes

AF:

0.00556

AC:

846

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00140

AC:

352

AN:

251396

Hom.:

AF XY:

0.000979

AC XY:

133

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0198

Gnomad AMR exome

AF:

0.000491

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000498

AC:

728

AN:

1461848

Hom.:

Cov.:

AF XY:

0.000396

AC XY:

288

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0177

Gnomad4 AMR exome

AF:

0.000604

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.00104

GnomAD4 genome

AF:

0.00558

AC:

850

AN:

152244

Hom.:

Cov.:

AF XY:

0.00541

AC XY:

403

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0195

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00142

Hom.:

Bravo

AF:

0.00641

ESP6500AA

AF:

0.0204

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00187

AC:

227

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

RNASET2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2024

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

0.071

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.14

DANN

Benign

0.50

DEOGEN2

Benign

0.0027

.;T;T;T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.38

T;.;T;T;T

MetaRNN

Benign

0.0040

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.48

.;N;.;N;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.11

N;N;.;N;N

REVEL

Benign

0.10

Sift

Benign

0.81

T;T;.;T;T

Sift4G

Benign

0.70

T;T;T;T;.

Polyphen

0.026

.;B;.;B;.

Vest4

0.017

MVP

0.27

MPC

0.22

ClinPred

0.0036

GERP RS

-6.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.031

gMVP

0.33

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