Variant 12-116833874-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001382266.1(RNFT2):c.965T>C(p.Met322Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,180 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RNFT2
NM_001382266.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.61

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNFT2	NM_001382266.1 linkuse as main transcript	c.965T>C	p.Met322Thr	missense_variant	8/11	ENST00000257575.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNFT2	ENST00000257575.9 linkuse as main transcript	c.965T>C	p.Met322Thr	missense_variant	8/11	5	NM_001382266.1	P1	Q96EX2-1
RNFT2	ENST00000392549.7 linkuse as main transcript	c.965T>C	p.Met322Thr	missense_variant	8/12	5		P1	Q96EX2-1
RNFT2	ENST00000407967.7 linkuse as main transcript	c.965T>C	p.Met322Thr	missense_variant	8/11	5			Q96EX2-5
RNFT2	ENST00000547718.5 linkuse as main transcript	c.*922T>C		3_prime_UTR_variant, NMD_transcript_variant	9/12	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250330

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135304

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726850

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 26, 2024

The c.965T>C (p.M322T) alteration is located in exon 8 (coding exon 7) of the RNFT2 gene. This alteration results from a T to C substitution at nucleotide position 965, causing the methionine (M) at amino acid position 322 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

0.22

BayesDel_addAF

Benign

-0.0014

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.051

T;T;.

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.88

.;D;D

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.58

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.93

N;N;N

REVEL

Benign

0.19

Sift

Benign

0.17

T;T;T

Sift4G

Uncertain

0.026

D;D;D

Polyphen

0.49

P;P;.

Vest4

0.86

MutPred

0.61

Loss of stability (P = 0.0025);Loss of stability (P = 0.0025);Loss of stability (P = 0.0025);

MVP

0.043

MPC

0.29

ClinPred

0.59

GERP RS

5.0

Varity_R

0.27

gMVP

0.89

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