dbSNP rs3807032: RNF39:c.-417G>C (chr6-30076002-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_025236.4(RNF39):c.-417G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 603,504 control chromosomes in the GnomAD database, including 8,293 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 0.19 ( 4240 hom., cov: 33)

Exomes 𝑓: 0.11 ( 4053 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
RNF39	NM_025236.4 link	c.-417G>C	upstream_gene_variant	ENST00000244360.8	NP_079512.3	Q9H2S5Q96QB5
RNF39	NM_170769.3 link	c.-417G>C	upstream_gene_variant		NP_739575.3	Q9H2S5A0A1U9X8G2
RNF39	XM_017011325.2 link	c.-649G>C	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>C		upstream_gene_variant		1	NM_025236.4	ENSP00000244360.7		Q9H2S5
RNF39	ENST00000376751.8 link	c.-417G>C		upstream_gene_variant		1		ENSP00000365942.4		Q9H2S5

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28549

AN:

152058

Hom.:

4232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.405

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.152

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.0264

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.0854

Gnomad OTH

AF:

0.213

GnomAD4 exome

AF:

0.112

AC:

50682

AN:

451326

Hom.:

4053

AF XY:

0.112

AC XY:

26816

AN XY:

238410

show subpopulations

African (AFR)

AF:

0.403

AC:

4972

AN:

12330

American (AMR)

AF:

0.208

AC:

3786

AN:

18206

Ashkenazi Jewish (ASJ)

AF:

0.166

AC:

2289

AN:

13788

East Asian (EAS)

AF:

0.171

AC:

5253

AN:

30774

South Asian (SAS)

AF:

0.152

AC:

6584

AN:

43380

European-Finnish (FIN)

AF:

0.0320

AC:

944

AN:

29500

Middle Eastern (MID)

AF:

0.193

AC:

424

AN:

2196

European-Non Finnish (NFE)

AF:

0.0833

AC:

22912

AN:

274962

Other (OTH)

AF:

0.134

AC:

3518

AN:

26190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

2197

4394

6592

8789

10986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

256

512

768

1024

1280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.188

AC:

28587

AN:

152178

Hom.:

4240

Cov.:

AF XY:

0.183

AC XY:

13603

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.404

AC:

16766

AN:

41476

American (AMR)

AF:

0.197

AC:

3009

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

597

AN:

3472

East Asian (EAS)

AF:

0.152

AC:

784

AN:

5160

South Asian (SAS)

AF:

0.170

AC:

821

AN:

4830

European-Finnish (FIN)

AF:

0.0264

AC:

280

AN:

10620

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0854

AC:

5807

AN:

67996

Other (OTH)

AF:

0.210

AC:

444

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1063

2127

3190

4254

5317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0391

Hom.:

Bravo

AF:

0.216

Asia WGS

AF:

0.161

AC:

560

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.11

(source)

DANN

Benign

0.73

PhyloP100

-2.7

PromoterAI

0.15

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over