Variant 17-59963203-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_016125.4(RNFT1):c.138C>T(p.His46His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00703 in 1,614,142 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0071 ( 42 hom. )

Consequence

RNFT1
NM_016125.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.40

Variant links:

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]

RNFT1 links:

ENSG00000267318 (HGNC:):

ENSG00000267318 links:

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]

TBC1D3P1-DHX40P1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 17-59963203-G-A is Benign according to our data. Variant chr17-59963203-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2647991.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.4 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNFT1	NM_016125.4 link	c.138C>T	p.His46His	synonymous_variant	2/9	ENST00000305783.13	NP_057209.3	Q5M7Z0-1
TBC1D3P1-DHX40P1	NR_002924.3 link	n.1288C>T		non_coding_transcript_exon_variant	13/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNFT1	ENST00000305783.13 link	c.138C>T	p.His46His	synonymous_variant	2/9	1	NM_016125.4	ENSP00000304670.8		Q5M7Z0-1
ENSG00000267318	ENST00000591035.1 link	c.150-3200G>A		intron_variant		3		ENSP00000468280.1		K7ERJ3

Frequencies

GnomAD3 genomes

AF:

0.00594

AC:

904

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00595

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00800

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00922

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00607

AC:

1522

AN:

250714

Hom.:

AF XY:

0.00609

AC XY:

826

AN XY:

135616

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.00387

Gnomad ASJ exome

AF:

0.00655

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00327

Gnomad FIN exome

AF:

0.00763

Gnomad NFE exome

AF:

0.00872

Gnomad OTH exome

AF:

0.00897

GnomAD4 exome

AF:

0.00714

AC:

10444

AN:

1461832

Hom.:

Cov.:

AF XY:

0.00707

AC XY:

5143

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00409

Gnomad4 ASJ exome

AF:

0.00700

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00312

Gnomad4 FIN exome

AF:

0.00661

Gnomad4 NFE exome

AF:

0.00801

Gnomad4 OTH exome

AF:

0.00730

GnomAD4 genome

AF:

0.00593

AC:

903

AN:

152310

Hom.:

Cov.:

AF XY:

0.00642

AC XY:

478

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00128

Gnomad4 AMR

AF:

0.00595

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.00800

Gnomad4 NFE

AF:

0.00922

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00851

Hom.:

Bravo

AF:

0.00559

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0103

EpiControl

AF:

0.00871

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

RNFT1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.5

DANN

Benign

0.19

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over