1-182585389-T-G

Variant summary

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

The NM_021133.4(RNASEL):c.1418A>C(p.Gln473Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNASEL NM_021133.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.514

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]

ACMG classification

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	UniProt
RNASEL	NM_021133.4	c.1418A>C	p.Gln473Pro	missense_variant	2/7	ENST00000367559.7
RNASEL	XM_047427096.1	c.1418A>C	p.Gln473Pro	missense_variant	2/7
RNASEL	XM_047427106.1	c.1418A>C	p.Gln473Pro	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNASEL	ENST00000367559.7	c.1418A>C	p.Gln473Pro	missense_variant	2/7	1	NM_021133.4	P1
RNASEL	ENST00000539397.1	c.1418A>C	p.Gln473Pro	missense_variant	2/6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer, hereditary, 1 Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Laboratory of Virology, Oncology, Biosciences and Environment, Faculty of Sciences and Techniques, Mohammedia- University Hassan II of Casablanca

Aug 17, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	18
Dann	Uncertain	0.98
DEOGEN2	Benign	0.30	T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.74	T;T
M_CAP	Uncertain	0.093	D
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.23
Sift	Uncertain	0.014	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		0.97	D;.
Vest4		0.32
MutPred		0.79		Gain of ubiquitination at K470 (P = 0.0837);Gain of ubiquitination at K470 (P = 0.0837);
MVP		0.81
MPC		0.31
ClinPred		0.59	D
GERP RS		-2.4
Varity_R		0.57
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-182554524;