Variant 14-20891900-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000304639.4(RNASE3):c.214C>T(p.Arg72Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00609 in 1,612,940 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0043 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 50 hom. )

Consequence

RNASE3
ENST00000304639.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.421

Variant links:

Genes affected

RNASE3 (HGNC:10046): (ribonuclease A family member 3) The protein encoded by this gene belongs to the pancreatic ribonuclease family, a subset of the ribonuclease A superfamily. The protein exhibits antimicrobial activity against pathogenic bacteria [provided by RefSeq, Oct 2014]

RNASE3 links:

LOC100507513 (HGNC:):

LOC100507513 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009386808).

BP6

Variant 14-20891900-C-T is Benign according to our data. Variant chr14-20891900-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2644053.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASE3	NM_002935.3 linkuse as main transcript	c.214C>T	p.Arg72Cys	missense_variant	2/2	ENST00000304639.4	NP_002926.2
LOC100507513	XR_110261.4 linkuse as main transcript	n.723-16157G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASE3	ENST00000304639.4 linkuse as main transcript	c.214C>T	p.Arg72Cys	missense_variant	2/2	1	NM_002935.3	ENSP00000302324	P1

Frequencies

GnomAD3 genomes

AF:

0.00434

AC:

657

AN:

151212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00341

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00747

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00433

AC:

1089

AN:

251340

Hom.:

AF XY:

0.00428

AC XY:

582

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00137

Gnomad FIN exome

AF:

0.00213

Gnomad NFE exome

AF:

0.00792

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00627

AC:

9161

AN:

1461610

Hom.:

Cov.:

AF XY:

0.00612

AC XY:

4453

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.000873

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00151

Gnomad4 FIN exome

AF:

0.00217

Gnomad4 NFE exome

AF:

0.00766

Gnomad4 OTH exome

AF:

0.00450

GnomAD4 genome

AF:

0.00434

AC:

657

AN:

151330

Hom.:

Cov.:

AF XY:

0.00430

AC XY:

318

AN XY:

73978

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.00341

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00747

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00630

Hom.:

Bravo

AF:

0.00411

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.00137

AC:

ESP6500EA

AF:

0.00663

AC:

ExAC

AF:

0.00466

AC:

566

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00616

EpiControl

AF:

0.00634

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

RNASE3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.0094

LIST_S2

Benign

0.83

M_CAP

Benign

0.0020

MetaRNN

Benign

0.0094

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.040

Sift

Uncertain

0.0060

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.13

MVP

0.26

MPC

0.27

ClinPred

0.048

GERP RS

-0.65

Varity_R

0.41

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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