rs1062070

chr6-32180254-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006913.4(RNF5):c.471A>G(p.Pro157=) 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 1,610,544 control chromosomes in the GnomAD database, including 25,815 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 (1678 hom., cov: 32)
  • Exomes 𝑓: 0.17 (24137 hom.)
• Consequence: RNF5 NM_006913.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-0.168 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/exons	MANE	UniProt
RNF5	NM_006913.4	c.471A>G	p.Pro157=	synonymous_variant	6/6	ENST00000375094.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF5	ENST00000375094.4	c.471A>G	p.Pro157=	synonymous_variant	6/6	1	NM_006913.4	P1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21548 AN: 151406 Hom.: 1683 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.0812

Gnomad ASJ AF: 0.0875

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.129

GnomAD3 exomes AF: 0.135 AC: 33207 AN: 246366 Hom.: 2555 AF XY: 0.137 AC XY: 18401 AN XY: 134252

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.0733

Gnomad ASJ exome AF: 0.0896

Gnomad EAS exome AF: 0.0909

Gnomad SAS exome AF: 0.130

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.170

Gnomad OTH exome AF: 0.131

GnomAD4 exome AF: 0.175 AC: 254928 AN: 1459018 Hom.: 24137 Cov.: 33 AF XY: 0.173 AC XY: 125354 AN XY: 725918

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.0771

Gnomad4 ASJ exome AF: 0.0930

Gnomad4 EAS exome AF: 0.0970

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.142 AC: 21537 AN: 151526 Hom.: 1678 Cov.: 32 AF XY: 0.138 AC XY: 10198 AN XY: 74072

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0808

Gnomad4 ASJ AF: 0.0875

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.128

Alfa AF: 0.158 Hom.: 1109

Bravo AF: 0.138

Asia WGS AF: 0.111 AC: 385 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	-0.77
Cadd	Benign	5.4
Dann	Benign	0.78

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: rs1062070; hg19: chr6-32148031; COSMIC: COSV61247641; COSMIC: COSV61247641;