rs4968401

Variant names:

• chr17-59963369-T-C
• rs4968401
• NM_016125.4:c.57-85A>G

Variant summary

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

The NM_016125.4(RNFT1):​c.57-85A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 1,134,166 control chromosomes in the GnomAD database, including 167,177 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 0.44 (16891 hom., cov: 31)
  • Exomes 𝑓: 0.55 (150286 hom.)
• Consequence: RNFT1 NM_016125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78
• Publications: 9 publications found

Genes affected

RNFT1 (HGNC:30206): (ring finger protein, transmembrane 1) Enables ubiquitin binding activity and ubiquitin protein ligase activity. Involved in positive regulation of ERAD pathway and protein autoubiquitination. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267318 (HGNC:):

TBC1D3P1-DHX40P1 (HGNC:42362): (TBC1D3P1-DHX40P1 readthrough, transcribed pseudogene) This locus represents naturally-occurring readthrough transcription that extends through two unprocessed pseudogenes, TBC1D3P1 (TBC1 domain family member 3 pseudogene 1) and DHX40P1 (DEAH-box helicase 40 pseudogene 1), to protein-coding RNFT1 (ring finger protein, transmembrane 1). The individual pseudogene loci are not curated as transcribed regions. The readthrough transcript likely does not encode a functional protein, since translation of the long open reading frames would render the transcript a candidate for nonsense-mediated decay (NMD). [provided by RefSeq, Jan 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016125.4. 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
	RNFT1	NM_016125.4	MANE Select	c.57-85A>G		intron	N/A	NP_057209.3
	TBC1D3P1-DHX40P1	NR_002924.3		n.1207-85A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNFT1	ENST00000305783.13	TSL:1 MANE Select	c.57-85A>G		intron	N/A	ENSP00000304670.8
	ENSG00000267318	ENST00000591035.1	TSL:3	c.150-3034T>C		intron	N/A	ENSP00000468280.1
	RNFT1	ENST00000477207.2	TSL:1	n.131-85A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67277 AN: 151816 Hom.: 16893 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.547 AC: 537304 AN: 982232 Hom.: 150286 AF XY: 0.549 AC XY: 272093 AN XY: 495396

African (AFR) AF: 0.179 AC: 4142 AN: 23148

American (AMR) AF: 0.554 AC: 16228 AN: 29288

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 10573 AN: 18300

East Asian (EAS) AF: 0.417 AC: 15460 AN: 37070

South Asian (SAS) AF: 0.572 AC: 35879 AN: 62708

European-Finnish (FIN) AF: 0.564 AC: 19331 AN: 34302

Middle Eastern (MID) AF: 0.472 AC: 2059 AN: 4358

European-Non Finnish (NFE) AF: 0.563 AC: 410499 AN: 729042

Other (OTH) AF: 0.526 AC: 23133 AN: 44016

GnomAD4 genome AF: 0.443 AC: 67281 AN: 151934 Hom.: 16891 Cov.: 31 AF XY: 0.446 AC XY: 33115 AN XY: 74232

African (AFR) AF: 0.189 AC: 7841 AN: 41442

American (AMR) AF: 0.470 AC: 7182 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2013 AN: 3464

East Asian (EAS) AF: 0.438 AC: 2266 AN: 5168

South Asian (SAS) AF: 0.577 AC: 2778 AN: 4812

European-Finnish (FIN) AF: 0.571 AC: 6022 AN: 10542

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37665 AN: 67928

Other (OTH) AF: 0.441 AC: 929 AN: 2106

Alfa AF: 0.496 Hom.: 2494

Bravo AF: 0.426

Asia WGS AF: 0.431 AC: 1499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.72
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4968401; hg19: chr17-58040730; COSMIC: COSV59870010; COSMIC: COSV59870010;