Variant 6-30071298-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_025236.4(RNF39):c.872A>G(p.Glu291Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 1,500,426 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 14 hom. )

Consequence

RNF39
NM_025236.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.908

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051576495).

BP6

Variant 6-30071298-T-C is Benign according to our data. Variant chr6-30071298-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2656332.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RNF39	NM_025236.4 linkuse as main transcript	c.872A>G	p.Glu291Gly	missense_variant	4/4	ENST00000244360.8
RNF39	XM_017011325.2 linkuse as main transcript	c.617A>G	p.Glu206Gly	missense_variant	3/3
RNF39	NM_170769.3 linkuse as main transcript	c.772-98A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF39	ENST00000244360.8 linkuse as main transcript	c.872A>G	p.Glu291Gly	missense_variant	4/4	1	NM_025236.4	P1
RNF39	ENST00000376751.8 linkuse as main transcript	c.772-98A>G		intron_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00273

AC:

415

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.00947

Gnomad SAS

AF:

0.00952

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00176

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00331

AC:

450

AN:

135774

Hom.:

AF XY:

0.00369

AC XY:

273

AN XY:

73988

show subpopulations

Gnomad AFR exome

AF:

0.000388

Gnomad AMR exome

AF:

0.00228

Gnomad ASJ exome

AF:

0.0168

Gnomad EAS exome

AF:

0.00541

Gnomad SAS exome

AF:

0.00815

Gnomad FIN exome

AF:

0.00397

Gnomad NFE exome

AF:

0.00203

Gnomad OTH exome

AF:

0.00382

GnomAD4 exome

AF:

0.00255

AC:

3438

AN:

1348216

Hom.:

Cov.:

AF XY:

0.00279

AC XY:

1840

AN XY:

659614

show subpopulations

Gnomad4 AFR exome

AF:

0.000848

Gnomad4 AMR exome

AF:

0.00224

Gnomad4 ASJ exome

AF:

0.0202

Gnomad4 EAS exome

AF:

0.00343

Gnomad4 SAS exome

AF:

0.0109

Gnomad4 FIN exome

AF:

0.00357

Gnomad4 NFE exome

AF:

0.00152

Gnomad4 OTH exome

AF:

0.00436

GnomAD4 genome

AF:

0.00272

AC:

414

AN:

152210

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

210

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.0225

Gnomad4 EAS

AF:

0.00950

Gnomad4 SAS

AF:

0.00932

Gnomad4 FIN

AF:

0.00433

Gnomad4 NFE

AF:

0.00177

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00221

Hom.:

Bravo

AF:

0.00238

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000342

AC:

ESP6500EA

AF:

0.00190

AC:

ExAC

AF:

0.00289

AC:

308

Asia WGS

AF:

0.00924

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

RNF39: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.00058

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.012

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.10

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.77

REVEL

Benign

0.069

Sift

Benign

0.35

Sift4G

Benign

0.37

Polyphen

0.0

Vest4

0.032

MVP

0.33

MPC

1.3

ClinPred

0.0012

GERP RS

3.1

Varity_R

0.054

gMVP

0.49

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