rs2301751

Positions:

• chr6-30071707-C-T

Variant summary

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

The NM_025236.4(RNF39):​c.479-16G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0489 in 1,397,300 control chromosomes in the GnomAD database, including 1,998 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 0.052 (257 hom., cov: 32)
  • Exomes 𝑓: 0.048 (1741 hom.)
• Consequence: RNF39 NM_025236.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF39	NM_025236.4	c.479-16G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000244360.8
RNF39	NM_170769.3	c.479-16G>A		splice_polypyrimidine_tract_variant, intron_variant
RNF39	XM_017011325.2	c.224-16G>A		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF39	ENST00000244360.8	c.479-16G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_025236.4	P1
RNF39	ENST00000376751.8	c.479-16G>A		splice_polypyrimidine_tract_variant, intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0519 AC: 7902 AN: 152114 Hom.: 256 Cov.: 32

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.0363

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0516

Gnomad OTH AF: 0.0598

GnomAD3 exomes AF: 0.0562 AC: 1086 AN: 19320 Hom.: 40 AF XY: 0.0563 AC XY: 573 AN XY: 10176

Gnomad AFR exome AF: 0.0689

Gnomad AMR exome AF: 0.0603

Gnomad ASJ exome AF: 0.186

Gnomad EAS exome AF: 0.0424

Gnomad SAS exome AF: 0.0316

Gnomad FIN exome AF: 0.0121

Gnomad NFE exome AF: 0.0648

Gnomad OTH exome AF: 0.0716

GnomAD4 exome AF: 0.0485 AC: 60346 AN: 1245068 Hom.: 1741 Cov.: 30 AF XY: 0.0482 AC XY: 29095 AN XY: 603332

Gnomad4 AFR exome AF: 0.0454

Gnomad4 AMR exome AF: 0.0606

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.0875

Gnomad4 SAS exome AF: 0.0247

Gnomad4 FIN exome AF: 0.0253

Gnomad4 NFE exome AF: 0.0469

Gnomad4 OTH exome AF: 0.0556

GnomAD4 genome AF: 0.0520 AC: 7916 AN: 152232 Hom.: 257 Cov.: 32 AF XY: 0.0518 AC XY: 3857 AN XY: 74422

Gnomad4 AFR AF: 0.0496

Gnomad4 AMR AF: 0.0678

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.0364

Gnomad4 SAS AF: 0.0237

Gnomad4 FIN AF: 0.0238

Gnomad4 NFE AF: 0.0516

Gnomad4 OTH AF: 0.0587

Alfa AF: 0.0563 Hom.: 193

Bravo AF: 0.0545

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.8
DANN	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2301751; hg19: chr6-30039484;