Genetic Variant NM_001382266.1:c.685C>T (chr12-116766871-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001382266.1(RNFT2):c.685C>T(p.Leu229Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L229V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RNFT2
NM_001382266.1 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16968516).

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>T	p.Leu229Phe	missense	Exon 6 of 11	NP_001369195.1	Q96EX2-1
RNFT2	NM_001109903.2		c.685C>T	p.Leu229Phe	missense	Exon 6 of 12	NP_001103373.1	Q96EX2-1
RNFT2	NM_032814.4		c.685C>T	p.Leu229Phe	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>T	p.Leu229Phe	missense	Exon 6 of 11	ENSP00000257575.4	Q96EX2-1
RNFT2	ENST00000392549.7	TSL:5	c.685C>T	p.Leu229Phe	missense	Exon 6 of 12	ENSP00000376332.2	Q96EX2-1
RNFT2	ENST00000407967.7	TSL:5	c.685C>T	p.Leu229Phe	missense	Exon 6 of 11	ENSP00000385669.3	Q96EX2-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000447

AC:

AN:

223508

AF XY:

0.00000836

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1444364

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716590

African (AFR)

AF:

0.00

AC:

AN:

33262

American (AMR)

AF:

0.00

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:

0.00

AC:

AN:

1103230

Other (OTH)

AF:

0.00

AC:

AN:

59856

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.062

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.76

M_CAP

Benign

0.012

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

-0.11

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.6

REVEL

Benign

0.10

Sift

Benign

0.28

Sift4G

Benign

0.21

Polyphen

0.76

Vest4

0.27

MutPred

0.35

Loss of helix (P = 0.0558)

MVP

0.11

MPC

0.26

ClinPred

0.22

GERP RS

2.8

Varity_R

0.036

gMVP

0.59

Mutation Taster

=70/30

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over