chr6-32180626-G-C

Position:

• chr6-32180626-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000375094.4(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 ENST00000375094.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

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 -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/exons	MANE	Protein	UniProt
RNF5	NM_006913.4	c.*300G>C		3_prime_UTR_variant	6/6	ENST00000375094.4	NP_008844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF5	ENST00000375094.4	c.*300G>C		3_prime_UTR_variant	6/6	1	NM_006913.4	ENSP00000364235	P1

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

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.0840

Gnomad4 ASJ exome AF: 0.0899

Gnomad4 EAS exome AF: 0.0941

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.147

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

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.0803

Gnomad4 ASJ AF: 0.0873

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.127

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
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: rs8365; hg19: chr6-32148403;