9-101540320-C-T

Variant names:

• chr9-101540320-C-T
• rs367537997
• NM_019592.7:c.247C>T

Variant summary

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

The NM_019592.7(RNF20):​c.247C>T​(p.Gln83*) variant causes a stop gained change involving the alteration of a 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 not provided (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF20 NM_019592.7 stop_gained
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 7.91
• Publications: 3 publications found

Genes affected

RNF20 (HGNC:10062): (ring finger protein 20) The protein encoded by this gene shares similarity with BRE1 of S. cerevisiae. The protein encoded by this human gene is an E3 ubiquitin ligase that regulates chromosome structure by monoubiquitinating histone H2B. This protein acts as a putative tumor suppressor and positively regulates the p53 tumor suppressor as well as numerous histone H2A and H2B genes. In contrast, this protein also suppresses the expression of several protooncogenes and growth-related genes, including many genes that are induced by epidermal growth factor. This gene selectively suppresses the expression of some genes by interfering with chromatin recruitment of transcription elongation factor SII (TFIIS). [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF20	NM_019592.7	c.247C>T	p.Gln83*	stop_gained	Exon 3 of 20	ENST00000389120.8	NP_062538.5
RNF20	XM_011518862.2	c.247C>T	p.Gln83*	stop_gained	Exon 3 of 20		XP_011517164.1
RNF20	XM_047423594.1	c.247C>T	p.Gln83*	stop_gained	Exon 4 of 21		XP_047279550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF20	ENST00000389120.8	c.247C>T	p.Gln83*	stop_gained	Exon 3 of 20	1	NM_019592.7	ENSP00000373772.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

Richard Lifton Laboratory, Yale University School of Medicine

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.58
CADD	Pathogenic	38
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0	.;.;.;.
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.0	.;.;.;.
MetaRNN	Benign	0.0	.;.;.;.
MutationAssessor	Benign	0.0	.;.;.;.
PhyloP100		7.9
PROVEAN	Benign	0.0	.;.;.;.
REVEL	Benign	0.0
Sift	Pathogenic	0.0	.;.;.;.
Sift4G	Pathogenic	0.0	.;.;.;.
Vest4		0.86
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=0/200	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs367537997; hg19: chr9-104302602;