rs3130349

Variant names:

• chr6-32179919-G-A
• rs3130349
• NM_006913.4:c.315G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-32179919-G-A
• chr6-32179919-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.77
• Publications: 58 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006913.4. 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
	RNF5	NM_006913.4	MANE Select	c.315G>A	p.Pro105Pro	synonymous	Exon 4 of 6	NP_008844.1
	MIR6833	NR_106891.1		n.*43G>A		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF5	ENST00000375094.4	TSL:1 MANE Select	c.315G>A	p.Pro105Pro	synonymous	Exon 4 of 6	ENSP00000364235.3
	RNF5	ENST00000876421.1		c.315G>A	p.Pro105Pro	synonymous	Exon 4 of 6	ENSP00000546480.1
	RNF5	ENST00000876424.1		c.309G>A	p.Pro103Pro	synonymous	Exon 4 of 6	ENSP00000546483.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21584 AN: 152090 Hom.: 1694 Cov.: 32

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

GnomAD2 exomes AF: 0.135 AC: 33832 AN: 250394 AF XY: 0.137

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 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.: 53 AF XY: 0.173 AC XY: 125685 AN XY: 727190

African (AFR) AF: 0.114 AC: 3812 AN: 33478

American (AMR) AF: 0.0771 AC: 3449 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0931 AC: 2432 AN: 26134

East Asian (EAS) AF: 0.0972 AC: 3858 AN: 39700

South Asian (SAS) AF: 0.130 AC: 11243 AN: 86254

European-Finnish (FIN) AF: 0.136 AC: 7291 AN: 53420

Middle Eastern (MID) AF: 0.0662 AC: 382 AN: 5768

European-Non Finnish (NFE) AF: 0.192 AC: 212979 AN: 1111890

Other (OTH) AF: 0.169 AC: 10233 AN: 60390

GnomAD4 genome AF: 0.142 AC: 21574 AN: 152208 Hom.: 1690 Cov.: 32 AF XY: 0.137 AC XY: 10218 AN XY: 74402

African (AFR) AF: 0.110 AC: 4571 AN: 41520

American (AMR) AF: 0.0805 AC: 1232 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0873 AC: 303 AN: 3470

East Asian (EAS) AF: 0.105 AC: 544 AN: 5176

South Asian (SAS) AF: 0.154 AC: 746 AN: 4830

European-Finnish (FIN) AF: 0.137 AC: 1454 AN: 10594

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12217 AN: 67998

Other (OTH) AF: 0.128 AC: 270 AN: 2114

Alfa AF: 0.169 Hom.: 10776

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.0
DANN	Benign	0.84
PhyloP100		-5.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs3130349; hg19: chr6-32147696; COSMIC: COSV61247636; COSMIC: COSV61247636;