Variant 6-30071128-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_025236.4(RNF39):c.1042G>C(p.Val348Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,553,876 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 35 hom. )

Consequence

RNF39
NM_025236.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.645

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007796854).

BS2

High Homozygotes in GnomAdExome4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RNF39	NM_025236.4 linkuse as main transcript	c.1042G>C	p.Val348Leu	missense_variant	4/4	ENST00000244360.8
RNF39	NM_170769.3 linkuse as main transcript	c.844G>C	p.Val282Leu	missense_variant	5/5
RNF39	XM_017011325.2 linkuse as main transcript	c.787G>C	p.Val263Leu	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF39	ENST00000244360.8 linkuse as main transcript	c.1042G>C	p.Val348Leu	missense_variant	4/4	1	NM_025236.4	P1
RNF39	ENST00000376751.8 linkuse as main transcript	c.844G>C	p.Val282Leu	missense_variant	5/5	1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00347

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000292

AC:

AN:

174822

Hom.:

AF XY:

0.000235

AC XY:

AN XY:

93616

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000320

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00212

Gnomad SAS exome

AF:

0.000104

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000134

Gnomad OTH exome

AF:

0.00178

GnomAD4 exome

AF:

0.000295

AC:

413

AN:

1401512

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

177

AN XY:

690830

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000259

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00190

Gnomad4 SAS exome

AF:

0.0000393

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000102

Gnomad4 OTH exome

AF:

0.00547

GnomAD4 genome

AF:

0.000249

AC:

AN:

152364

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00348

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.0000435

Hom.:

Bravo

AF:

0.000378

ExAC

AF:

0.000172

AC:

Asia WGS

AF:

0.0300

AC:

104

AN:

3478

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

Dec 11, 2023

The c.1246G>C (p.V416L) alteration is located in exon 4 (coding exon 4) of the RNF39 gene. This alteration results from a G to C substitution at nucleotide position 1246, causing the valine (V) at amino acid position 416 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

Benign

0.24

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0017

.;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.72

MetaRNN

Benign

0.0078

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.040

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.85

N;N

REVEL

Benign

0.050

Sift

Benign

0.079

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.0080

B;B

Vest4

0.096

MutPred

0.64

.;Gain of disorder (P = 0.0938);

MVP

0.25

MPC

1.2

ClinPred

0.022

GERP RS

3.5

Varity_R

0.031

gMVP

0.62

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