9-101544770-A-G

Variant names:

• chr9-101544770-A-G
• rs761046832
• NM_019592.7:c.632A>G

Variant summary

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

The NM_019592.7(RNF20):​c.632A>G​(p.Asn211Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/26 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N211T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RNF20 NM_019592.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530
• Publications: 0 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

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF20	NM_019592.7	MANE Select	c.632A>G	p.Asn211Ser	missense	Exon 6 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.632A>G	p.Asn211Ser	missense	Exon 6 of 20	ENSP00000373772.3
	RNF20	ENST00000888393.1		c.632A>G	p.Asn211Ser	missense	Exon 6 of 20	ENSP00000558452.1
	RNF20	ENST00000888394.1		c.632A>G	p.Asn211Ser	missense	Exon 7 of 21	ENSP00000558453.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441668 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 718674

African (AFR) AF: 0.00 AC: 0 AN: 33086

American (AMR) AF: 0.0000224 AC: 1 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26000

East Asian (EAS) AF: 0.00 AC: 0 AN: 39600

South Asian (SAS) AF: 0.00 AC: 0 AN: 85842

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1093608

Other (OTH) AF: 0.00 AC: 0 AN: 59784

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.9
DANN	Benign	0.61
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.053
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.023
Sift	Benign	1.0	T
Sift4G	Benign	0.95	T
Polyphen		0.0	B
Vest4		0.063
MutPred		0.23		Gain of phosphorylation at N211 (P = 0.042)
MVP		0.23
MPC		0.68
ClinPred		0.10	T
GERP RS		-0.58
Varity_R		0.0090
gMVP		0.036
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.35		Position offset: 1
DS_AL_spliceai		0.30		Position offset: -3

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

Other links and lift over

dbSNP: rs761046832; hg19: chr9-104307052;