Variant 6-30071139-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025236.4(RNF39):c.1031C>T(p.Pro344Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000712 in 1,545,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

RNF39
NM_025236.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16147262).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RNF39	NM_025236.4 linkuse as main transcript	c.1031C>T	p.Pro344Leu	missense_variant	4/4	ENST00000244360.8
RNF39	NM_170769.3 linkuse as main transcript	c.833C>T	p.Pro278Leu	missense_variant	5/5
RNF39	XM_017011325.2 linkuse as main transcript	c.776C>T	p.Pro259Leu	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF39	ENST00000244360.8 linkuse as main transcript	c.1031C>T	p.Pro344Leu	missense_variant	4/4	1	NM_025236.4	P1
RNF39	ENST00000376751.8 linkuse as main transcript	c.833C>T	p.Pro278Leu	missense_variant	5/5	1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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:

0.0000234

AC:

AN:

171188

Hom.:

AF XY:

0.0000328

AC XY:

AN XY:

91460

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000369

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000200

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:

0.00000431

AC:

AN:

1393570

Hom.:

Cov.:

AF XY:

0.00000729

AC XY:

AN XY:

685588

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000105

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000186

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000172

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

Dec 15, 2023

The c.1235C>T (p.P412L) alteration is located in exon 4 (coding exon 4) of the RNF39 gene. This alteration results from a C to T substitution at nucleotide position 1235, causing the proline (P) at amino acid position 412 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

0.16

BayesDel_addAF

Benign

-0.0043

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

.;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.12

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.5

.;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-4.2

D;D

REVEL

Benign

0.25

Sift

Pathogenic

0.0

D;T

Sift4G

Uncertain

0.013

D;D

Polyphen

0.66

P;B

Vest4

0.17

MutPred

0.67

.;Loss of disorder (P = 0.0385);

MVP

0.48

MPC

1.2

ClinPred

0.41

GERP RS

2.4

Varity_R

0.030

gMVP

0.77

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