1-182585378-A-T

Variant names:

• chr1-182585378-A-T
• rs2102369789
• NM_021133.4:c.1429T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021133.4(RNASEL):​c.1429T>A​(p.Leu477Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 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: -0.440

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13218251).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASEL	NM_021133.4	c.1429T>A	p.Leu477Met	missense_variant	Exon 2 of 7	ENST00000367559.7	NP_066956.1
RNASEL	XM_047427096.1	c.1429T>A	p.Leu477Met	missense_variant	Exon 2 of 7		XP_047283052.1
RNASEL	XM_047427106.1	c.1429T>A	p.Leu477Met	missense_variant	Exon 2 of 6		XP_047283062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559.7	c.1429T>A	p.Leu477Met	missense_variant	Exon 2 of 7	1	NM_021133.4	ENSP00000356530.3
RNASEL	ENST00000539397.1	c.1429T>A	p.Leu477Met	missense_variant	Exon 2 of 6	2		ENSP00000440844.1

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

Aug 17, 2022

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

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	4.8
DANN	Benign	0.65
DEOGEN2	Benign	0.039	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.40	T;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.50	N;N
REVEL	Benign	0.17
Sift	Benign	0.15	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.27	B;.
Vest4		0.16
MutPred		0.48		Gain of catalytic residue at L477 (P = 0.002);Gain of catalytic residue at L477 (P = 0.002);
MVP		0.66
MPC		0.092
ClinPred		0.18	T
GERP RS		-11
Varity_R		0.14
gMVP		0.067
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs2102369789; hg19: chr1-182554513;