Variant 1-182581247-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021133.4(RNASEL):c.1883G>A(p.Ser628Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,106 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Consequence

RNASEL
NM_021133.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.182

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASEL	NM_021133.4 linkuse as main transcript	c.1883G>A	p.Ser628Asn	missense_variant	5/7	ENST00000367559.7	NP_066956.1	Q05823-1
RNASEL	XM_047427096.1 linkuse as main transcript	c.1883G>A	p.Ser628Asn	missense_variant	5/7		XP_047283052.1
RNASEL	XM_047427106.1 linkuse as main transcript	c.1883G>A	p.Ser628Asn	missense_variant	5/6		XP_047283062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559.7 linkuse as main transcript	c.1883G>A	p.Ser628Asn	missense_variant	5/7	1	NM_021133.4	ENSP00000356530.3		Q05823-1
RNASEL	ENST00000539397.1 linkuse as main transcript	c.1883G>A	p.Ser628Asn	missense_variant	5/6	2		ENSP00000440844.1		Q05823-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 22, 2023

The c.1883G>A (p.S628N) alteration is located in exon 5 (coding exon 4) of the RNASEL gene. This alteration results from a G to A substitution at nucleotide position 1883, causing the serine (S) at amino acid position 628 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

T;.

Eigen

Benign

-0.082

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.45

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.99

N;N

REVEL

Benign

0.12

Sift

Benign

0.12

T;T

Sift4G

Benign

0.065

T;T

Polyphen

0.32

B;.

Vest4

0.44

MutPred

0.54

Loss of phosphorylation at S628 (P = 0.0485);Loss of phosphorylation at S628 (P = 0.0485);

MVP

0.65

MPC

0.16

ClinPred

0.41

GERP RS

1.9

Varity_R

0.37

gMVP

0.15

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