Genetic Variant RNF39:c.-417G>A (chr6-30076002-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025236.4(RNF39):c.-417G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 451,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

RNF39
NM_025236.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.65

Publications

10 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
RNF39	NM_025236.4 link	c.-417G>A	upstream_gene_variant	ENST00000244360.8	NP_079512.3	Q9H2S5Q96QB5
RNF39	NM_170769.3 link	c.-417G>A	upstream_gene_variant		NP_739575.3	Q9H2S5A0A1U9X8G2
RNF39	XM_017011325.2 link	c.-649G>A	upstream_gene_variant		XP_016866814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF39	ENST00000244360.8 link	c.-417G>A		upstream_gene_variant		1	NM_025236.4	ENSP00000244360.7		Q9H2S5
RNF39	ENST00000376751.8 link	c.-417G>A		upstream_gene_variant		1		ENSP00000365942.4		Q9H2S5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000111

AC:

AN:

451488

Hom.:

AF XY:

0.0000126

AC XY:

AN XY:

238490

show subpopulations

African (AFR)

AF:

0.000243

AC:

AN:

12346

American (AMR)

AF:

0.00

AC:

AN:

18222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13788

East Asian (EAS)

AF:

0.00

AC:

AN:

30788

South Asian (SAS)

AF:

0.00

AC:

AN:

43398

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29500

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2196

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

275048

Other (OTH)

AF:

0.0000763

AC:

AN:

26202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.595

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.13

(source)

DANN

Benign

0.88

PhyloP100

-2.7

PromoterAI

0.0046

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over