dbSNP rs146270391: RNFT2:p.Leu229Val (chr12-116766871-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 15/22 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

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.047717392).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382266.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNFT2	NM_001382266.1	MANE Select	c.685C>G	p.Leu229Val	missense	Exon 6 of 11	NP_001369195.1	Q96EX2-1
RNFT2	NM_001109903.2		c.685C>G	p.Leu229Val	missense	Exon 6 of 12	NP_001103373.1	Q96EX2-1
RNFT2	NM_032814.4		c.685C>G	p.Leu229Val	missense	Exon 6 of 11	NP_116203.2	Q96EX2-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNFT2	ENST00000257575.9	TSL:5 MANE Select	c.685C>G	p.Leu229Val	missense	Exon 6 of 11	ENSP00000257575.4	Q96EX2-1
RNFT2	ENST00000392549.7	TSL:5	c.685C>G	p.Leu229Val	missense	Exon 6 of 12	ENSP00000376332.2	Q96EX2-1
RNFT2	ENST00000407967.7	TSL:5	c.685C>G	p.Leu229Val	missense	Exon 6 of 11	ENSP00000385669.3	Q96EX2-5

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

GnomAD2 exomes

AF:

0.0000582

AC:

AN:

223508

AF XY:

0.0000251

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 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

African (AFR)

AF:

0.000872

AC:

AN:

33262

American (AMR)

AF:

0.000119

AC:

AN:

42030

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25700

East Asian (EAS)

AF:

0.00

AC:

AN:

39122

South Asian (SAS)

AF:

0.00

AC:

AN:

82966

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52448

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

9.06e-7

AC:

AN:

1103230

Other (OTH)

AF:

0.0000668

AC:

AN:

59856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000256

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.000844

AC:

AN:

41448

American (AMR)

AF:

0.000196

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.028

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.85

M_CAP

Benign

0.0075

MetaRNN

Benign

0.048

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.21

PhyloP100

-0.11

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.28

REVEL

Benign

0.076

Sift

Benign

0.63

Sift4G

Benign

0.65

Polyphen

0.16

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

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over