chr6-30073232-A-G

Variant names:

• chr6-30073232-A-G
• rs2074479
• NM_025236.4:c.403T>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.403T>C​(p.Ser135Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,610,110 control chromosomes in the GnomAD database, including 15,772 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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 (2720 hom., cov: 31)
  • Exomes 𝑓: 0.12 (13052 hom.)
• Consequence: RNF39 NM_025236.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.871
• Publications: 43 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 (MetaRNN=0.0042379797).
• 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.403T>C	p.Ser135Pro	missense	Exon 3 of 4	NP_079512.3
	RNF39	NM_170769.3		c.403T>C	p.Ser135Pro	missense	Exon 3 of 5	NP_739575.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF39	ENST00000244360.8	TSL:1 MANE Select	c.403T>C	p.Ser135Pro	missense	Exon 3 of 4	ENSP00000244360.7
	RNF39	ENST00000376751.8	TSL:1	c.403T>C	p.Ser135Pro	missense	Exon 3 of 5	ENSP00000365942.4

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25838 AN: 151860 Hom.: 2703 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.0478

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.193

GnomAD2 exomes AF: 0.152 AC: 38074 AN: 249892 AF XY: 0.148

Gnomad AFR exome AF: 0.271

Gnomad AMR exome AF: 0.222

Gnomad ASJ exome AF: 0.297

Gnomad EAS exome AF: 0.205

Gnomad FIN exome AF: 0.0479

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.120 AC: 175440 AN: 1458132 Hom.: 13052 Cov.: 30 AF XY: 0.122 AC XY: 88310 AN XY: 725602

African (AFR) AF: 0.274 AC: 9132 AN: 33330

American (AMR) AF: 0.222 AC: 9943 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 7639 AN: 26080

East Asian (EAS) AF: 0.250 AC: 9921 AN: 39676

South Asian (SAS) AF: 0.166 AC: 14338 AN: 86154

European-Finnish (FIN) AF: 0.0501 AC: 2674 AN: 53418

Middle Eastern (MID) AF: 0.166 AC: 957 AN: 5758

European-Non Finnish (NFE) AF: 0.101 AC: 111830 AN: 1108750

Other (OTH) AF: 0.149 AC: 9006 AN: 60252

GnomAD4 genome AF: 0.170 AC: 25890 AN: 151978 Hom.: 2720 Cov.: 31 AF XY: 0.168 AC XY: 12512 AN XY: 74318

African (AFR) AF: 0.274 AC: 11339 AN: 41370

American (AMR) AF: 0.211 AC: 3219 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3472

East Asian (EAS) AF: 0.189 AC: 978 AN: 5170

South Asian (SAS) AF: 0.183 AC: 879 AN: 4814

European-Finnish (FIN) AF: 0.0478 AC: 506 AN: 10594

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7428 AN: 67950

Other (OTH) AF: 0.192 AC: 406 AN: 2112

Alfa AF: 0.140 Hom.: 8219

Bravo AF: 0.191

TwinsUK AF: 0.0998 AC: 370

ALSPAC AF: 0.0859 AC: 331

ESP6500AA AF: 0.255 AC: 772

ESP6500EA AF: 0.120 AC: 650

ExAC AF: 0.152 AC: 18476

Asia WGS AF: 0.210 AC: 732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.042
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.60
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.011	N
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.63	N
PhyloP100		0.87
PrimateAI	Benign	0.40	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.029
MPC		0.0021
ClinPred		0.00030	T
GERP RS		4.0
Varity_R		0.090
gMVP		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2074479; hg19: chr6-30041009; COSMIC: COSV54994846; COSMIC: COSV54994846;