rs9393989

Variant names:

• chr6-30072307-G-A
• rs9393989
• NM_025236.4:c.479-616C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025236.4(RNF39):​c.479-616C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 151,842 control chromosomes in the GnomAD database, including 4,995 homozygotes. 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: 𝑓 0.25 (4995 hom., cov: 30)
• Consequence: RNF39 NM_025236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 24 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF39	NM_025236.4	c.479-616C>T		intron_variant	Intron 3 of 3	ENST00000244360.8	NP_079512.3
RNF39	NM_170769.3	c.479-616C>T		intron_variant	Intron 3 of 4		NP_739575.3
RNF39	XM_017011325.2	c.224-616C>T		intron_variant	Intron 2 of 2		XP_016866814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF39	ENST00000244360.8	c.479-616C>T		intron_variant	Intron 3 of 3	1	NM_025236.4	ENSP00000244360.7
RNF39	ENST00000376751.8	c.479-616C>T		intron_variant	Intron 3 of 4	1		ENSP00000365942.4

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37783 AN: 151724 Hom.: 4994 Cov.: 30

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.219

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.249 AC: 37791 AN: 151842 Hom.: 4995 Cov.: 30 AF XY: 0.250 AC XY: 18539 AN XY: 74210

African (AFR) AF: 0.187 AC: 7727 AN: 41412

American (AMR) AF: 0.238 AC: 3633 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 573 AN: 3468

East Asian (EAS) AF: 0.294 AC: 1510 AN: 5144

South Asian (SAS) AF: 0.162 AC: 777 AN: 4806

European-Finnish (FIN) AF: 0.358 AC: 3773 AN: 10548

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.280 AC: 19019 AN: 67876

Other (OTH) AF: 0.217 AC: 457 AN: 2110

Alfa AF: 0.264 Hom.: 15075

Bravo AF: 0.240

Asia WGS AF: 0.192 AC: 669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.4
DANN	Benign	0.40
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9393989; hg19: chr6-30040084;