NM_018683.4:c.*251G>T

Variant names:

• chr20-49952392-G-T
• rs6125829
• NM_018683.4:c.*251G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018683.4(RNF114):​c.*251G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 539,326 control chromosomes in the GnomAD database, including 47,035 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 0.35 (11068 hom., cov: 32)
  • Exomes 𝑓: 0.42 (35967 hom.)
• Consequence: RNF114 NM_018683.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374
• Publications: 25 publications found

Genes affected

RNF114 (HGNC:13094): (ring finger protein 114) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein polyubiquitination and ubiquitin-dependent protein catabolic process. Located in cytosol and plasma membrane. Biomarker of male infertility. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018683.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF114	NM_018683.4	MANE Select	c.*251G>T		3_prime_UTR	Exon 6 of 6	NP_061153.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF114	ENST00000244061.6	TSL:1 MANE Select	c.*251G>T		3_prime_UTR	Exon 6 of 6	ENSP00000244061.2
	RNF114	ENST00000622999.3	TSL:2	n.*766G>T		non_coding_transcript_exon	Exon 6 of 6	ENSP00000485203.1
	RNF114	ENST00000622920.1	TSL:5	c.*150G>T		3_prime_UTR	Exon 5 of 5	ENSP00000485317.1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53218 AN: 151820 Hom.: 11052 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.358

GnomAD4 exome AF: 0.421 AC: 163221 AN: 387388 Hom.: 35967 Cov.: 0 AF XY: 0.428 AC XY: 86640 AN XY: 202274

African (AFR) AF: 0.126 AC: 1466 AN: 11646

American (AMR) AF: 0.456 AC: 7704 AN: 16886

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 3881 AN: 12232

East Asian (EAS) AF: 0.339 AC: 10059 AN: 29686

South Asian (SAS) AF: 0.561 AC: 17930 AN: 31978

European-Finnish (FIN) AF: 0.558 AC: 15359 AN: 27510

Middle Eastern (MID) AF: 0.332 AC: 577 AN: 1740

European-Non Finnish (NFE) AF: 0.418 AC: 97292 AN: 232822

Other (OTH) AF: 0.391 AC: 8953 AN: 22888

GnomAD4 genome AF: 0.351 AC: 53268 AN: 151938 Hom.: 11068 Cov.: 32 AF XY: 0.365 AC XY: 27065 AN XY: 74238

African (AFR) AF: 0.126 AC: 5215 AN: 41448

American (AMR) AF: 0.441 AC: 6731 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1134 AN: 3468

East Asian (EAS) AF: 0.343 AC: 1768 AN: 5156

South Asian (SAS) AF: 0.559 AC: 2692 AN: 4816

European-Finnish (FIN) AF: 0.564 AC: 5948 AN: 10542

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28641 AN: 67936

Other (OTH) AF: 0.359 AC: 758 AN: 2112

Alfa AF: 0.371 Hom.: 12950

Bravo AF: 0.324

Asia WGS AF: 0.459 AC: 1597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.8
DANN	Benign	0.75
PhyloP100		0.37
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: rs6125829; hg19: chr20-48568929; COSMIC: COSV54871437; COSMIC: COSV54871437;