rs8365

Variant names:

• chr6-32180626-G-C
• rs8365
• NM_006913.4:c.*300G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006913.4(RNF5):​c.*300G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 445,354 control chromosomes in the GnomAD database, including 5,357 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 (1688 hom., cov: 32)
  • Exomes 𝑓: 0.15 (3669 hom.)
• Consequence: RNF5 NM_006913.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• Publications: 27 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• 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	c.*300G>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000375094.4	NP_008844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF5	ENST00000375094.4	c.*300G>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_006913.4	ENSP00000364235.3

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21563 AN: 151942 Hom.: 1693 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.0807

Gnomad ASJ AF: 0.0873

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.146 AC: 42925 AN: 293292 Hom.: 3669 Cov.: 0 AF XY: 0.145 AC XY: 21892 AN XY: 150994

African (AFR) AF: 0.106 AC: 940 AN: 8874

American (AMR) AF: 0.0840 AC: 842 AN: 10028

Ashkenazi Jewish (ASJ) AF: 0.0899 AC: 894 AN: 9944

East Asian (EAS) AF: 0.0941 AC: 2056 AN: 21852

South Asian (SAS) AF: 0.111 AC: 2361 AN: 21306

European-Finnish (FIN) AF: 0.133 AC: 2485 AN: 18742

Middle Eastern (MID) AF: 0.0708 AC: 105 AN: 1484

European-Non Finnish (NFE) AF: 0.167 AC: 30555 AN: 182764

Other (OTH) AF: 0.147 AC: 2687 AN: 18298

GnomAD4 genome AF: 0.142 AC: 21553 AN: 152062 Hom.: 1688 Cov.: 32 AF XY: 0.137 AC XY: 10205 AN XY: 74332

African (AFR) AF: 0.110 AC: 4572 AN: 41456

American (AMR) AF: 0.0803 AC: 1227 AN: 15276

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

East Asian (EAS) AF: 0.104 AC: 539 AN: 5182

South Asian (SAS) AF: 0.154 AC: 740 AN: 4818

European-Finnish (FIN) AF: 0.138 AC: 1456 AN: 10578

Middle Eastern (MID) AF: 0.0890 AC: 26 AN: 292

European-Non Finnish (NFE) AF: 0.180 AC: 12211 AN: 67970

Other (OTH) AF: 0.127 AC: 268 AN: 2108

Alfa AF: 0.168 Hom.: 291

Bravo AF: 0.138

Asia WGS AF: 0.113 AC: 395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	14
DANN	Benign	0.82
PhyloP100		2.1
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)		0.0		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: rs8365; hg19: chr6-32148403;