rs3134945

Positions:

• chr6-32178715-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006913.4(RNF5):​c.140+64C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,507,000 control chromosomes in the GnomAD database, including 33,346 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 0.18 (2642 hom., cov: 31)
  • Exomes 𝑓: 0.20 (30704 hom.)
• Consequence: RNF5 NM_006913.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.576

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF5	NM_006913.4	c.140+64C>A		intron_variant		ENST00000375094.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF5	ENST00000375094.4	c.140+64C>A		intron_variant		1	NM_006913.4	P1
RNF5	ENST00000487940.1	n.215+64C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27518 AN: 151776 Hom.: 2645 Cov.: 31

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0430

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.203 AC: 275264 AN: 1355106 Hom.: 30704 AF XY: 0.200 AC XY: 135360 AN XY: 677718

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.0937

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.0235

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.181 AC: 27513 AN: 151894 Hom.: 2642 Cov.: 31 AF XY: 0.174 AC XY: 12926 AN XY: 74242

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.0431

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.168

Alfa AF: 0.200 Hom.: 3602

Bravo AF: 0.182

Asia WGS AF: 0.0900 AC: 313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.7
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs3134945; hg19: chr6-32146492;