Variant 6-166929697-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1

The NM_003730.6(RNASET2):c.662C>A(p.Ser221Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000263 in 1,614,130 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

RNASET2
NM_003730.6 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.404

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 -14 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0053533316).

BP6

Variant 6-166929697-G-T is Benign according to our data. Variant chr6-166929697-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 712409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00129 (196/152258) while in subpopulation AFR AF= 0.00416 (173/41558). AF 95% confidence interval is 0.00366. There are 1 homozygotes in gnomad4. There are 95 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASET2	NM_003730.6 link	c.662C>A	p.Ser221Tyr	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.662C>A	p.Ser221Tyr	missense_variant	9/9	1	NM_003730.6	ENSP00000426455.2		O00584-1
ENSG00000249141	ENST00000507747.1 link	c.432+4394C>A		intron_variant		5		ENSP00000426906.1		H0YAE9

Frequencies

GnomAD3 genomes

AF:

0.00129

AC:

196

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00418

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000302

AC:

AN:

251426

Hom.:

AF XY:

0.000213

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00369

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000157

AC:

229

AN:

1461872

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

100

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00478

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.00129

AC:

196

AN:

152258

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00416

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000280

Hom.:

Bravo

AF:

0.00147

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000354

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Benign

7.2

DANN

Benign

0.95

DEOGEN2

Benign

0.067

.;T;T;T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.63

T;.;T;T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.0054

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.0

.;M;.;M;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.9

N;N;.;N;N

REVEL

Benign

0.22

Sift

Benign

0.10

T;T;.;T;T

Sift4G

Uncertain

0.037

D;D;D;D;.

Polyphen

0.74

.;P;.;P;.

Vest4

0.19

MVP

0.80

MPC

0.30

ClinPred

0.018

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.061

gMVP

0.35

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