Variant 6-30071277-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_025236.4(RNF39):c.893G>T(p.Arg298Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000266 in 1,504,786 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

RNF39
NM_025236.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.63

Variant links:

Genes affected

RNF39 (HGNC:18064): (ring finger protein 39) This gene lies within the major histocompatibility complex class I region on chromosome 6. Studies of a similar rat protein suggest that this gene encodes a protein that plays a role in an early phase of synaptic plasticity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RNF39 links:

Genome browser will be placed here

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
RNF39	NM_025236.4 linkuse as main transcript	c.893G>T	p.Arg298Leu	missense_variant	4/4	ENST00000244360.8
RNF39	XM_017011325.2 linkuse as main transcript	c.638G>T	p.Arg213Leu	missense_variant	3/3
RNF39	NM_170769.3 linkuse as main transcript	c.772-77G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF39	ENST00000244360.8 linkuse as main transcript	c.893G>T	p.Arg298Leu	missense_variant	4/4	1	NM_025236.4	P1
RNF39	ENST00000376751.8 linkuse as main transcript	c.772-77G>T		intron_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000897

AC:

AN:

144904

Hom.:

AF XY:

0.0000635

AC XY:

AN XY:

78732

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000540

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000709

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000295

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000288

AC:

AN:

1352564

Hom.:

Cov.:

AF XY:

0.0000257

AC XY:

AN XY:

661768

show subpopulations

Gnomad4 AFR exome

AF:

0.0000337

Gnomad4 AMR exome

AF:

0.000404

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:

0.0000236

Gnomad4 OTH exome

AF:

0.0000361

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74370

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.0000462

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

Mar 15, 2024

The c.1097G>T (p.R366L) alteration is located in exon 4 (coding exon 4) of the RNF39 gene. This alteration results from a G to T substitution at nucleotide position 1097, causing the arginine (R) at amino acid position 366 to be replaced by a leucine (L). 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

Pathogenic

0.73

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.68

M_CAP

Pathogenic

0.92

MetaRNN

Uncertain

0.51

MetaSVM

Uncertain

-0.15

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-4.6

REVEL

Uncertain

0.57

Sift

Benign

0.082

Sift4G

Uncertain

0.022

Polyphen

0.91

Vest4

0.31

MutPred

0.75

Loss of MoRF binding (P = 0.0256);

MVP

0.74

MPC

2.2

ClinPred

0.44

GERP RS

4.4

Varity_R

0.32

gMVP

0.85

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