6-32179984-T-C

Variant names:

• chr6-32179984-T-C
• rs3134943
• NM_006913.4:c.328-25T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006913.4(RNF5):​c.328-25T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 1,614,088 control chromosomes in the GnomAD database, including 610,563 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 0.89 (60698 hom., cov: 34)
  • Exomes 𝑓: 0.87 (549865 hom.)
• Consequence: RNF5 NM_006913.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481
• Publications: 49 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.926 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.328-25T>C		intron	N/A	NP_008844.1	Q99942
	MIR6833	NR_106891.1		n.*108T>C		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.328-25T>C		intron	N/A	ENSP00000364235.3	Q99942
	RNF5	ENST00000876421.1		c.328-25T>C		intron	N/A	ENSP00000546480.1
	RNF5	ENST00000876424.1		c.322-25T>C		intron	N/A	ENSP00000546483.1

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135695 AN: 152172 Hom.: 60647 Cov.: 34

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.915

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.912

GnomAD2 exomes AF: 0.887 AC: 223023 AN: 251378 AF XY: 0.888

Gnomad AFR exome AF: 0.934

Gnomad AMR exome AF: 0.918

Gnomad ASJ exome AF: 0.971

Gnomad EAS exome AF: 0.876

Gnomad FIN exome AF: 0.872

Gnomad NFE exome AF: 0.864

Gnomad OTH exome AF: 0.887

GnomAD4 exome AF: 0.867 AC: 1266664 AN: 1461798 Hom.: 549865 Cov.: 51 AF XY: 0.868 AC XY: 631293 AN XY: 727208

African (AFR) AF: 0.936 AC: 31338 AN: 33480

American (AMR) AF: 0.916 AC: 40946 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.968 AC: 25287 AN: 26136

East Asian (EAS) AF: 0.920 AC: 36538 AN: 39700

South Asian (SAS) AF: 0.904 AC: 77961 AN: 86258

European-Finnish (FIN) AF: 0.867 AC: 46328 AN: 53420

Middle Eastern (MID) AF: 0.902 AC: 5201 AN: 5768

European-Non Finnish (NFE) AF: 0.855 AC: 950803 AN: 1111922

Other (OTH) AF: 0.865 AC: 52262 AN: 60392

GnomAD4 genome AF: 0.892 AC: 135801 AN: 152290 Hom.: 60698 Cov.: 34 AF XY: 0.893 AC XY: 66504 AN XY: 74458

African (AFR) AF: 0.934 AC: 38806 AN: 41548

American (AMR) AF: 0.914 AC: 14001 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.965 AC: 3351 AN: 3472

East Asian (EAS) AF: 0.878 AC: 4549 AN: 5180

South Asian (SAS) AF: 0.888 AC: 4290 AN: 4830

European-Finnish (FIN) AF: 0.883 AC: 9373 AN: 10614

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.858 AC: 58386 AN: 68016

Other (OTH) AF: 0.911 AC: 1925 AN: 2114

Alfa AF: 0.873 Hom.: 244384

Bravo AF: 0.898

Asia WGS AF: 0.861 AC: 2998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.30
PhyloP100		-0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3134943; hg19: chr6-32147761;