6-166929711-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003730.6(RNASET2):c.648G>A(p.Pro216=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,614,046 control chromosomes in the GnomAD database, including 1,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P216P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.041 ( 360 hom., cov: 33)

Exomes 𝑓: 0.0088 ( 673 hom. )

Consequence

RNASET2
NM_003730.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.91

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 6-166929711-C-T is Benign according to our data. Variant chr6-166929711-C-T is described in ClinVar as [Benign]. Clinvar id is 356029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-166929711-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.91 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNASET2	NM_003730.6 linkuse as main transcript	c.648G>A	p.Pro216=	synonymous_variant	9/9	ENST00000508775.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNASET2	ENST00000508775.6 linkuse as main transcript	c.648G>A	p.Pro216=	synonymous_variant	9/9	1	NM_003730.6	P1	O00584-1

Frequencies

GnomAD3 genomes

AF:

0.0414

AC:

6296

AN:

152068

Hom.:

358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.0912

Gnomad AMR

AF:

0.0185

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.0780

Gnomad SAS

AF:

0.0230

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.0288

GnomAD3 exomes

AF:

0.0189

AC:

4762

AN:

251412

Hom.:

222

AF XY:

0.0167

AC XY:

2272

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.135

Gnomad AMR exome

AF:

0.00945

Gnomad ASJ exome

AF:

0.00347

Gnomad EAS exome

AF:

0.0688

Gnomad SAS exome

AF:

0.0238

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00109

Gnomad OTH exome

AF:

0.0124

GnomAD4 exome

AF:

0.00884

AC:

12921

AN:

1461860

Hom.:

673

Cov.:

AF XY:

0.00886

AC XY:

6444

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.138

Gnomad4 AMR exome

AF:

0.0103

Gnomad4 ASJ exome

AF:

0.00356

Gnomad4 EAS exome

AF:

0.0992

Gnomad4 SAS exome

AF:

0.0223

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

0.000738

Gnomad4 OTH exome

AF:

0.0165

GnomAD4 genome

AF:

0.0415

AC:

6313

AN:

152186

Hom.:

360

Cov.:

AF XY:

0.0409

AC XY:

3042

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.0184

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.0781

Gnomad4 SAS

AF:

0.0233

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.0308

Alfa

AF:

0.00790

Hom.:

Bravo

AF:

0.0468

Asia WGS

AF:

0.0670

AC:

233

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cystic leukoencephalopathy without megalencephaly

Benign:1

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

Cadd

Benign

0.011

Dann

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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