chr6-30071463-G-T

Variant names:

• chr6-30071463-G-T
• rs2301753
• NM_025236.4:c.707C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025236.4(RNF39):​c.707C>A​(p.Ala236Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,556,918 control chromosomes in the GnomAD database, including 15,551 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 (2738 hom., cov: 33)
  • Exomes 𝑓: 0.12 (12813 hom.)
• Consequence: RNF39 NM_025236.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 41 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=0.0032743216).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF39	NM_025236.4	MANE Select	c.707C>A	p.Ala236Glu	missense	Exon 4 of 4	NP_079512.3
	RNF39	NM_170769.3		c.707C>A	p.Ala236Glu	missense	Exon 4 of 5	NP_739575.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF39	ENST00000244360.8	TSL:1 MANE Select	c.707C>A	p.Ala236Glu	missense	Exon 4 of 4	ENSP00000244360.7	Q9H2S5
	RNF39	ENST00000376751.8	TSL:1	c.707C>A	p.Ala236Glu	missense	Exon 4 of 5	ENSP00000365942.4	Q9H2S5

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25905 AN: 152094 Hom.: 2721 Cov.: 33

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: 0.0476

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.193

GnomAD2 exomes AF: 0.176 AC: 28845 AN: 164144 AF XY: 0.170

Gnomad AFR exome AF: 0.309

Gnomad AMR exome AF: 0.249

Gnomad ASJ exome AF: 0.323

Gnomad EAS exome AF: 0.240

Gnomad FIN exome AF: 0.0540

Gnomad NFE exome AF: 0.126

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.122 AC: 171319 AN: 1404706 Hom.: 12813 Cov.: 32 AF XY: 0.124 AC XY: 86135 AN XY: 697348

African (AFR) AF: 0.284 AC: 8616 AN: 30298

American (AMR) AF: 0.238 AC: 8926 AN: 37482

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 7278 AN: 24260

East Asian (EAS) AF: 0.260 AC: 9417 AN: 36278

South Asian (SAS) AF: 0.171 AC: 13760 AN: 80456

European-Finnish (FIN) AF: 0.0514 AC: 2096 AN: 40746

Middle Eastern (MID) AF: 0.168 AC: 948 AN: 5628

European-Non Finnish (NFE) AF: 0.102 AC: 111450 AN: 1091442

Other (OTH) AF: 0.152 AC: 8828 AN: 58116

GnomAD4 genome AF: 0.171 AC: 25957 AN: 152212 Hom.: 2738 Cov.: 33 AF XY: 0.168 AC XY: 12533 AN XY: 74398

African (AFR) AF: 0.274 AC: 11394 AN: 41536

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: 971 AN: 5142

South Asian (SAS) AF: 0.183 AC: 882 AN: 4826

European-Finnish (FIN) AF: 0.0476 AC: 505 AN: 10610

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

European-Non Finnish (NFE) AF: 0.109 AC: 7445 AN: 68016

Other (OTH) AF: 0.192 AC: 406 AN: 2114

Alfa AF: 0.141 Hom.: 2989

Bravo AF: 0.191

TwinsUK AF: 0.0982 AC: 364

ALSPAC AF: 0.0854 AC: 329

ESP6500AA AF: 0.251 AC: 753

ESP6500EA AF: 0.118 AC: 637

ExAC AF: 0.143 AC: 16432

Asia WGS AF: 0.211 AC: 733 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.91
DEOGEN2	Benign	0.00036	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0069	N
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.2	N
PhyloP100		1.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.54	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.054
MPC		1.3
ClinPred		0.012	T
GERP RS		4.5
Varity_R		0.051
gMVP		0.12
Mutation Taster		=99/1	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: rs2301753; hg19: chr6-30039240; COSMIC: COSV54993334; COSMIC: COSV54993334;