NM_019592.7:c.379C>T

Variant names:

• chr9-101540571-C-T
• rs758664591
• NM_019592.7:c.379C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019592.7(RNF20):​c.379C>T​(p.Leu127Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RNF20 NM_019592.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.495
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1913726).

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.379C>T	p.Leu127Phe	missense	Exon 4 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.379C>T	p.Leu127Phe	missense	Exon 4 of 20	ENSP00000373772.3
	RNF20	ENST00000888393.1		c.379C>T	p.Leu127Phe	missense	Exon 4 of 20	ENSP00000558452.1
	RNF20	ENST00000888394.1		c.379C>T	p.Leu127Phe	missense	Exon 5 of 21	ENSP00000558453.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461870 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	0.0064	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.073	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.011
FATHMM_MKL	Benign	0.35	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.49
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.14
Sift	Benign	0.31	T
Sift4G	Benign	0.25	T
Polyphen		1.0	D
Vest4		0.42
MutPred		0.22		Loss of disorder (P = 0.1516)
MVP		0.64
MPC		0.62
ClinPred		0.79	D
GERP RS		4.3
Varity_R		0.050
gMVP		0.18
Mutation Taster		=74/26	polymorphism

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: rs758664591; hg19: chr9-104302853;