Variant 1-182585338-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PP5_ModerateBS2_Supporting

The NM_021133.4(RNASEL):c.1469A>G(p.Asn490Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

RNASEL
NM_021133.4 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 4.80

Variant links:

Genes affected

RNASEL (HGNC:10050): (ribonuclease L) This gene encodes a component of the interferon-regulated 2-5A system that functions in the antiviral and antiproliferative roles of interferons. The protein is involved in innate immunity and is active against multiple RNA viruses, including the influenza and SARS-CoV-2 viruses. Mutations in this gene have been associated with predisposition to prostate cancer and this gene is a candidate for the hereditary prostate cancer 1 (HPC1) allele. [provided by RefSeq, Nov 2021]

RNASEL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP5

Variant 1-182585338-T-C is Pathogenic according to our data. Variant chr1-182585338-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2445376.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 8 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASEL	NM_021133.4 linkuse as main transcript	c.1469A>G	p.Asn490Ser	missense_variant	2/7	ENST00000367559.7	NP_066956.1	Q05823-1
RNASEL	XM_047427096.1 linkuse as main transcript	c.1469A>G	p.Asn490Ser	missense_variant	2/7		XP_047283052.1
RNASEL	XM_047427106.1 linkuse as main transcript	c.1469A>G	p.Asn490Ser	missense_variant	2/6		XP_047283062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559.7 linkuse as main transcript	c.1469A>G	p.Asn490Ser	missense_variant	2/7	1	NM_021133.4	ENSP00000356530.3		Q05823-1
RNASEL	ENST00000539397.1 linkuse as main transcript	c.1469A>G	p.Asn490Ser	missense_variant	2/6	2		ENSP00000440844.1		Q05823-2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000916

AC:

AN:

251142

Hom.:

AF XY:

0.0000958

AC XY:

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00125

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461710

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000554

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Ovarian cancer

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University

Jan 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;.

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.97

D;D

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

3.8

H;H

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.1

N;N

REVEL

Uncertain

0.59

Sift

Uncertain

0.0060

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.69

MutPred

0.82

Loss of catalytic residue at N490 (P = 0.0501);Loss of catalytic residue at N490 (P = 0.0501);

MVP

1.0

MPC

0.33

ClinPred

0.53

GERP RS

6.0

Varity_R

0.65

gMVP

0.61

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