6-30073033-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025236.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF39	NM_025236.4	MANE Select	c.478+124A>C		intron	N/A	NP_079512.3
	RNF39	NM_170769.3		c.478+124A>C		intron	N/A	NP_739575.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF39	ENST00000244360.8	TSL:1 MANE Select	c.478+124A>C		intron	N/A	ENSP00000244360.7
	RNF39	ENST00000376751.8	TSL:1	c.478+124A>C		intron	N/A	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

African (AFR) AF: 0.265 AC: 3886 AN: 14672

American (AMR) AF: 0.212 AC: 5628 AN: 26536

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 4454 AN: 15608

East Asian (EAS) AF: 0.251 AC: 8591 AN: 34162

South Asian (SAS) AF: 0.164 AC: 8694 AN: 52958

European-Finnish (FIN) AF: 0.0512 AC: 1992 AN: 38890

Middle Eastern (MID) AF: 0.161 AC: 606 AN: 3774

European-Non Finnish (NFE) AF: 0.109 AC: 35125 AN: 321030

Other (OTH) AF: 0.153 AC: 4509 AN: 29454

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

African (AFR) AF: 0.274 AC: 11379 AN: 41482

American (AMR) AF: 0.210 AC: 3209 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1046 AN: 3462

East Asian (EAS) AF: 0.186 AC: 964 AN: 5186

South Asian (SAS) AF: 0.182 AC: 878 AN: 4816

European-Finnish (FIN) AF: 0.0477 AC: 506 AN: 10618

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.109 AC: 7442 AN: 68010

Other (OTH) AF: 0.188 AC: 397 AN: 2112

Alfa AF: 0.144 Hom.: 5063

Bravo AF: 0.190

Asia WGS AF: 0.180 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.43
PhyloP100		0.52
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: rs2074480; hg19: chr6-30040810;