rs200163867

Variant names:

• chr9-101546824-C-G
• rs200163867
• NM_019592.7:c.752C>G
• RNF20 p.Ser251Cys

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

0 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 0 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_SupportingB3_Supporting

The NM_019592.7(RNF20):c.752C>G (p.Ser251Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The gene RNF20 is a tumor suppressor gene (CancerMine: 3 TSG citations). The variant allele was found at a cumulative frequency of 0.0000192 (AC=31) in the gnomAD database across 1,613,840 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.0000191. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: RNF20 NM_019592.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.95
• Publications: 1 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]

Classification according to ACGS-UK Somatic Oncogenicity v2025

Our verdict: Uncertain_significance. The variant received 0 points.

• O3: Very rare in gnomAD (popmax AF <0.01%) — O3 supporting; GnomAD effective popmax AF = 0.000019 — very rare (O3 supporting [+1])
• B3: Computational evidence does not support a deleterious effect; Missense variant — primary computational scorer does not support an oncogenic/deleterious effect; supports B3

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_019592.7. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF20	NM_019592.7	MANE Select	c.752C>G	p.Ser251Cys	missense	Exon 7 of 20	NP_062538.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF20	ENST00000389120.8	TSL:1 MANE Select	c.752C>G	p.Ser251Cys	missense	Exon 7 of 20	ENSP00000373772.3	Q5VTR2
	RNF20	ENST00000888393.1		c.752C>G	p.Ser251Cys	missense	Exon 7 of 20	ENSP00000558452.1	Q5VTR2
	RNF20	ENST00000888394.1		c.752C>G	p.Ser251Cys	missense	Exon 8 of 21	ENSP00000558453.1	Q5VTR2

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	0.00000658	1	0	152082	32
GnomAD2 exomes	0.00000796	2		251332
GnomAD4 exome	0.0000205	30	0	1461758	31
GnomAD4 genome	0.00000658	1	0	152082	32
TOPMed (Bravo)	0.00000756	2	0	264690
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	0.00	0	0	13470
Local & regional cohorts 1 source Population-specific and national genomic databases
UK10K	0.000264	2		7562

Showing 7 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
BipEx(Bipolar disorder (including schizoaffective))	0.0000352	1	28400	0.00	0	28826
Epi25(Epilepsy)	0.00	0	41956	0.0000748	5	66876
SCHEMA(Schizophrenia)	0.00000967	1	103362	0.0000162	3	184644

Showing 3 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
AlphaGenome AVI	Pathogenic	-	20
AlphaMissense	Benign	-	0.090
BayesDel_addAF	Benign	T	-0.12
BayesDel_noAF	Benign	-	-0.40
CADD	Uncertain	-	23
DANN	Benign	-	0.96
DEOGEN2	Benign	T	0.36
Eigen	Benign	-	0.022
Eigen_PC	Benign	-	0.10
FATHMM_MKL	Uncertain	D	0.89
FuncVEP CTI	Benign	-	0.015
GPN-Star LLR	N/A	-	-3.2
GPN-Star score	N/A	-	3.2
LIST_S2	Benign	T	0.71
M_CAP	Benign	D	0.064
MetaRNN	Benign	T	0.25
MetaSVM	Benign	T	-0.73
Mutation Taster	N/A	polymorphism	84/16
MutationAssessor	Uncertain	M	2.0
PhyloP100	Benign	-	2.9
popEVE	Benign	-	-3.6
PrimateAI	Uncertain	T	0.49
PROVEAN	Uncertain	N	-2.5
RBP_binding_hub_radar	N/A	-	0.0
RBP_regulation_power_radar	N/A	-	1.1
REVEL	Benign	-	0.24
Sift	Benign	T	0.064
Sift4G	Uncertain	D	0.034
Varity_R	N/A	-	0.075
VESM-3B	Benign	-	-7.2

Showing 30 of 30 scores

Splicing Scores

Algorithm	Calibrated prediction	Prediction	Score
Pangolin (max)	Benign	-	0.010
SpliceAI score (max)	Benign	- Details are displayed if max score is > 0.2	0.0

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs200163867;

hg19: chr9-104309106;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar