Variant chr6-30071187-A-G 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.983T>C(p.Leu328Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000854 in 1,521,536 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000080 ( 0 hom. )

Consequence

RNF39
NM_025236.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.62

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.983T>C	p.Leu328Pro	missense_variant	4/4	ENST00000244360.8
RNF39	NM_170769.3 linkuse as main transcript	c.785T>C	p.Leu262Pro	missense_variant	5/5
RNF39	XM_017011325.2 linkuse as main transcript	c.728T>C	p.Leu243Pro	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF39	ENST00000244360.8 linkuse as main transcript	c.983T>C	p.Leu328Pro	missense_variant	4/4	1	NM_025236.4	P1
RNF39	ENST00000376751.8 linkuse as main transcript	c.785T>C	p.Leu262Pro	missense_variant	5/5	1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152218

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000640

AC:

AN:

156342

Hom.:

AF XY:

0.00

AC XY:

AN XY:

83696

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000458

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000803

AC:

AN:

1369318

Hom.:

Cov.:

AF XY:

0.00000744

AC XY:

AN XY:

671686

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000322

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:

0.00000561

Gnomad4 OTH exome

AF:

0.0000533

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

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

Aug 28, 2023

The c.1187T>C (p.L396P) alteration is located in exon 4 (coding exon 4) of the RNF39 gene. This alteration results from a T to C substitution at nucleotide position 1187, causing the leucine (L) at amino acid position 396 to be replaced by a proline (P). 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

0.21

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

.;T

Eigen

Benign

0.058

Eigen_PC

Benign

-0.057

FATHMM_MKL

Benign

0.24

M_CAP

Pathogenic

0.56

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.7

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.0

N;D

REVEL

Benign

0.24

Sift

Benign

0.10

T;T

Sift4G

Uncertain

0.0090

D;T

Polyphen

0.99

D;D

Vest4

0.29

MutPred

0.63

.;Gain of disorder (P = 0.0177);

MVP

0.65

MPC

2.5

ClinPred

0.62

GERP RS

3.1

Varity_R

0.23

gMVP

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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