NM_021133.4:c.3G>C

Variant names:

• chr1-182586804-C-G
• NM_021133.4:c.3G>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Moderate PS1_Moderate PM2

The NM_021133.4(RNASEL):​c.3G>C​(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNASEL NM_021133.4 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.01

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 Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Start lost variant, next in-frame start position is after 1 pathogenic variants. Next in-frame start position is after 69 codons. Genomic position: 182586602. Lost 0.092 part of the original CDS.
• PS1: Another start lost variant in NM_021133.4 (RNASEL) was described as [Pathogenic] in ClinVar as 13005
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASEL	NM_021133.4	c.3G>C	p.Met1?	start_lost	Exon 2 of 7	ENST00000367559.7	NP_066956.1
RNASEL	XM_047427096.1	c.3G>C	p.Met1?	start_lost	Exon 2 of 7		XP_047283052.1
RNASEL	XM_047427106.1	c.3G>C	p.Met1?	start_lost	Exon 2 of 6		XP_047283062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASEL	ENST00000367559.7	c.3G>C	p.Met1?	start_lost	Exon 2 of 7	1	NM_021133.4	ENSP00000356530.3
RNASEL	ENST00000539397.1	c.3G>C	p.Met1?	start_lost	Exon 2 of 6	2		ENSP00000440844.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.60	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;.
Eigen	Benign	-0.086
Eigen_PC	Benign	-0.036
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Uncertain	0.26	D
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-0.79	N;N
REVEL	Benign	0.28
Sift	Uncertain	0.014	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		0.24	B;.
Vest4		0.96
MutPred		0.99		Gain of stability (P = 0.0523);Gain of stability (P = 0.0523);
MVP		0.68
ClinPred		0.96	D
GERP RS		3.9
Varity_R		0.48
gMVP		0.65

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: chr1-182555939;