chr1-182585395-G-A

Position:

• chr1-182585395-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_021133.4(RNASEL):​c.1412C>T​(p.Ala471Val) 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 pathogenic 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: 3.28

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.789

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASEL	NM_021133.4	c.1412C>T	p.Ala471Val	missense_variant	2/7	ENST00000367559.7	NP_066956.1
RNASEL	XM_047427096.1	c.1412C>T	p.Ala471Val	missense_variant	2/7		XP_047283052.1
RNASEL	XM_047427106.1	c.1412C>T	p.Ala471Val	missense_variant	2/6		XP_047283062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559.7	c.1412C>T	p.Ala471Val	missense_variant	2/7	1	NM_021133.4	ENSP00000356530.3
RNASEL	ENST00000539397.1	c.1412C>T	p.Ala471Val	missense_variant	2/6	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

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.081	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	0.86	N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.5	N;N
REVEL	Uncertain	0.41
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		0.98	D;.
Vest4		0.55
MutPred		0.82		Gain of methylation at K470 (P = 0.0391);Gain of methylation at K470 (P = 0.0391);
MVP		0.94
MPC		0.34
ClinPred		0.87	D
GERP RS		2.9
Varity_R		0.22
gMVP		0.36

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: chr1-182554530;