Variant 17-59958388-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016125.4(RNFT1):c.749T>C(p.Ile250Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000493 in 1,603,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

RNFT1
NM_016125.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.51

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060110003).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNFT1	NM_016125.4 linkuse as main transcript	c.749T>C	p.Ile250Thr	missense_variant	5/9	ENST00000305783.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNFT1	ENST00000305783.13 linkuse as main transcript	c.749T>C	p.Ile250Thr	missense_variant	5/9	1	NM_016125.4	P1	Q5M7Z0-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000108

AC:

AN:

239764

Hom.:

AF XY:

0.000100

AC XY:

AN XY:

129722

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000919

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.0000531

AC:

AN:

1450802

Hom.:

Cov.:

AF XY:

0.0000693

AC XY:

AN XY:

721308

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000882

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.0000500

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.00116

AC:

AN:

3472

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.749T>C (p.I250T) alteration is located in exon 5 (coding exon 5) of the RNFT1 gene. This alteration results from a T to C substitution at nucleotide position 749, causing the isoleucine (I) at amino acid position 250 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.46

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.069

T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.5

N;.

REVEL

Benign

0.14

Sift

Benign

0.041

D;.

Sift4G

Benign

0.14

T;T

Polyphen

0.0

B;.

Vest4

0.60

MutPred

0.52

Loss of sheet (P = 0.0457);.;

MVP

0.54

MPC

0.21

ClinPred

0.11

GERP RS

4.1

Varity_R

0.095

gMVP

0.39

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