dbSNP rs3130349: RNF5:p.Pro105Pro (chr6-32179919-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_006913.4(RNF5):c.315G>A(p.Pro105Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,613,960 control chromosomes in the GnomAD database, including 25,823 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1690 hom., cov: 32)

Exomes 𝑓: 0.17 ( 24133 hom. )

Consequence

RNF5
NM_006913.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.77

Variant links:

Genes affected

RNF5 (HGNC:10068): (ring finger protein 5) The protein encoded by this gene contains a RING finger, which is a motif known to be involved in protein-protein interactions. This protein is a membrane-bound ubiquitin ligase. It can regulate cell motility by targeting paxillin ubiquitination and altering the distribution and localization of paxillin in cytoplasm and cell focal adhesions. [provided by RefSeq, Jul 2008]

RNF5 links:

MIR6833 (HGNC:50245): (microRNA 6833) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6833 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP7

Synonymous conserved (PhyloP=-5.77 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF5	NM_006913.4 link	c.315G>A	p.Pro105Pro	synonymous_variant	Exon 4 of 6	ENST00000375094.4	NP_008844.1	Q99942A0A024RCQ4
MIR6833	NR_106891.1 link	n.*43G>A		downstream_gene_variant
MIR6833	unassigned_transcript_1105	n.*77G>A		downstream_gene_variant
MIR6833	unassigned_transcript_1106	n.*43G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RNF5	ENST00000375094.4 link	c.315G>A	p.Pro105Pro	synonymous_variant	Exon 4 of 6	1	NM_006913.4	ENSP00000364235.3	Q99942
RNF5	ENST00000487940.1 link	n.*146G>A		downstream_gene_variant		2
MIR6833	ENST00000620680.1 link	n.*43G>A		downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21584

AN:

152090

Hom.:

1694

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.0809

Gnomad ASJ

AF:

0.0873

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.129

GnomAD3 exomes

AF:

0.135

AC:

33832

AN:

250394

Hom.:

2603

AF XY:

0.137

AC XY:

18588

AN XY:

135448

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.0734

Gnomad ASJ exome

AF:

0.0895

Gnomad EAS exome

AF:

0.0918

Gnomad SAS exome

AF:

0.130

Gnomad FIN exome

AF:

0.133

Gnomad NFE exome

AF:

0.170

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.175

AC:

255679

AN:

1461752

Hom.:

24133

Cov.:

AF XY:

0.173

AC XY:

125685

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.0771

Gnomad4 ASJ exome

AF:

0.0931

Gnomad4 EAS exome

AF:

0.0972

Gnomad4 SAS exome

AF:

0.130

Gnomad4 FIN exome

AF:

0.136

Gnomad4 NFE exome

AF:

0.192

Gnomad4 OTH exome

AF:

0.169

GnomAD4 genome

AF:

0.142

AC:

21574

AN:

152208

Hom.:

1690

Cov.:

AF XY:

0.137

AC XY:

10218

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.0805

Gnomad4 ASJ

AF:

0.0873

Gnomad4 EAS

AF:

0.105

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.180

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.167

Hom.:

4661

Bravo

AF:

0.138

Asia WGS

AF:

0.111

AC:

388

AN:

3478

EpiCase

AF:

0.175

EpiControl

AF:

0.160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.0

DANN

Benign

0.84

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over