rs433623

chr5-141988333-G-Achr5-141988333-G-T

Variant summary

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

The NM_004290.5(RNF14):c.*543G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 152,498 control chromosomes in the GnomAD database, including 23,875 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 0.54 (23775 hom., cov: 32)
  • Exomes 𝑓: 0.60 (100 hom.)
• Consequence: RNF14 NM_004290.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357

Genes affected

RNF14 (HGNC:10058): (ring finger protein 14) The protein encoded by this gene contains a RING zinc finger, a motif known to be involved in protein-protein interactions. This protein interacts with androgen receptor (AR) and may function as a coactivator that induces AR target gene expression in prostate. A dominant negative mutant of this gene has been demonstrated to inhibit the AR-mediated growth of prostate cancer. This protein also interacts with class III ubiquitin-conjugating enzymes (E2s) and may act as a ubiquitin-ligase (E3) in the ubiquitination of certain nuclear proteins. Six alternatively spliced transcript variants encoding two distinct isoforms have been reported. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF14	NM_004290.5	c.*543G>A		3_prime_UTR_variant	9/9	ENST00000394520.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF14	ENST00000394520.7	c.*543G>A		3_prime_UTR_variant	9/9	1	NM_004290.5	P1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81739 AN: 151856 Hom.: 23770 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.571

GnomAD4 exome AF: 0.599 AC: 314 AN: 524 Hom.: 100 Cov.: 0 AF XY: 0.599 AC XY: 182 AN XY: 304

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.703

Gnomad4 EAS exome AF: 0.600

Gnomad4 SAS exome AF: 0.679

Gnomad4 NFE exome AF: 0.574

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.538 AC: 81766 AN: 151974 Hom.: 23775 Cov.: 32 AF XY: 0.546 AC XY: 40523 AN XY: 74274

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.977

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.570

Alfa AF: 0.572 Hom.: 21817

Bravo AF: 0.538

Asia WGS AF: 0.772 AC: 2679 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.59
Dann	Benign	0.68
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: rs433623; hg19: chr5-141367898;