9-101540571-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.495

Publications

0 publications found

Variant links:

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]

RNF20 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
RNF20	NM_019592.7 link	c.379C>T	p.Leu127Phe	missense_variant	Exon 4 of 20	ENST00000389120.8	NP_062538.5
RNF20	XM_011518862.2 link	c.379C>T	p.Leu127Phe	missense_variant	Exon 4 of 20		XP_011517164.1
RNF20	XM_047423594.1 link	c.379C>T	p.Leu127Phe	missense_variant	Exon 5 of 21		XP_047279550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
RNF20	ENST00000389120.8 link	c.379C>T	p.Leu127Phe	missense_variant	Exon 4 of 20	1	NM_019592.7	ENSP00000373772.3
RNF20	ENST00000374819.6 link	c.379C>T	p.Leu127Phe	missense_variant	Exon 4 of 5	2		ENSP00000363952.2
RNF20	ENST00000466817.1 link	c.379C>T	p.Leu127Phe	missense_variant	Exon 4 of 4	5		ENSP00000418924.1
RNF20	ENST00000479306.5 link	c.*201C>T		downstream_gene_variant		5		ENSP00000419201.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 10, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.379C>T (p.L127F) alteration is located in exon 4 (coding exon 3) of the RNF20 gene. This alteration results from a C to T substitution at nucleotide position 379, causing the leucine (L) at amino acid position 127 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

0.0064

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.073

T;.;T

Eigen

Benign

0.13

Eigen_PC

Benign

0.011

FATHMM_MKL

Benign

0.35

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.2

L;.;.

PhyloP100

0.49

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.98

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.31

T;T;D

Sift4G

Benign

0.25

T;T;T

Vest4

0.42

ClinPred

0.79

GERP RS

4.3

Varity_R

0.050

gMVP

0.18

Mutation Taster

=74/26

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over