Variant 12-116766871-C-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_001382266.1(RNFT2):c.685C>G(p.Leu229Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000489 in 1,596,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

RNFT2
NM_001382266.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.114

Variant links:

Genes affected

RNFT2 (HGNC:25905): (ring finger protein, transmembrane 2) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in positive regulation of ERAD pathway and protein ubiquitination. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

RNFT2 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=0.047717392).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNFT2	NM_001382266.1 linkuse as main transcript	c.685C>G	p.Leu229Val	missense_variant	6/11	ENST00000257575.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNFT2	ENST00000257575.9 linkuse as main transcript	c.685C>G	p.Leu229Val	missense_variant	6/11	5	NM_001382266.1	P1	Q96EX2-1

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000582

AC:

AN:

223508

Hom.:

AF XY:

0.0000251

AC XY:

AN XY:

119638

show subpopulations

Gnomad AFR exome

AF:

0.000636

Gnomad AMR exome

AF:

0.0000958

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000177

GnomAD4 exome

AF:

0.0000270

AC:

AN:

1444364

Hom.:

Cov.:

AF XY:

0.0000195

AC XY:

AN XY:

716590

show subpopulations

Gnomad4 AFR exome

AF:

0.000872

Gnomad4 AMR exome

AF:

0.000119

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.06e-7

Gnomad4 OTH exome

AF:

0.0000668

GnomAD4 genome

AF:

0.000256

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.000844

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000378

Hom.:

Bravo

AF:

0.000385

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000660

AC:

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

Feb 02, 2024

The c.685C>G (p.L229V) alteration is located in exon 6 (coding exon 5) of the RNFT2 gene. This alteration results from a C to G substitution at nucleotide position 685, causing the leucine (L) at amino acid position 229 to be replaced by a valine (V). 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

0.070

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.028

T;T;.;T;T

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.85

.;T;T;D;D

M_CAP

Benign

0.0075

MetaRNN

Benign

0.048

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.21

N;N;N;.;.

MutationTaster

Benign

0.97

D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.28

N;N;N;.;N

REVEL

Benign

0.076

Sift

Benign

0.63

T;T;T;.;T

Sift4G

Benign

0.65

T;T;T;T;T

Polyphen

0.16

B;B;.;.;.

Vest4

0.53

MVP

0.093

MPC

0.24

ClinPred

0.0097

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.025

gMVP

0.47

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