6-30073033-T-G

Variant names:

• chr6-30073033-T-G
• rs2074480
• NM_025236.4:c.478+124A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025236.4(RNF39):​c.478+124A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 689,262 control chromosomes in the GnomAD database, including 9,042 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 0.17 (2728 hom., cov: 32)
  • Exomes 𝑓: 0.14 (6314 hom.)
• Consequence: RNF39 NM_025236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF39	NM_025236.4	c.478+124A>C		intron_variant	Intron 3 of 3	ENST00000244360.8	NP_079512.3
RNF39	NM_170769.3	c.478+124A>C		intron_variant	Intron 3 of 4		NP_739575.3
RNF39	XM_017011325.2	c.223+124A>C		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.478+124A>C		intron_variant	Intron 3 of 3	1	NM_025236.4	ENSP00000244360.7
RNF39	ENST00000376751.8	c.478+124A>C		intron_variant	Intron 3 of 4	1		ENSP00000365942.4

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25858 AN: 152060 Hom.: 2712 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.137 AC: 73485 AN: 537084 Hom.: 6314 AF XY: 0.137 AC XY: 39461 AN XY: 287028

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.251

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.0512

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.170 AC: 25904 AN: 152178 Hom.: 2728 Cov.: 32 AF XY: 0.168 AC XY: 12522 AN XY: 74420

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.0477

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.188

Alfa AF: 0.135 Hom.: 1494

Bravo AF: 0.190

Asia WGS AF: 0.180 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs2074480; hg19: chr6-30040810;