rs2074479

Positions:

• chr6-30073232-A-C
• chr6-30073232-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025236.4(RNF39):​c.403T>G​(p.Ser135Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: RNF39 NM_025236.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.871

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07870054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF39	NM_025236.4	c.403T>G	p.Ser135Ala	missense_variant	3/4	ENST00000244360.8	NP_079512.3
RNF39	NM_170769.3	c.403T>G	p.Ser135Ala	missense_variant	3/5		NP_739575.3
RNF39	XM_017011325.2	c.148T>G	p.Ser50Ala	missense_variant	2/3		XP_016866814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF39	ENST00000244360.8	c.403T>G	p.Ser135Ala	missense_variant	3/4	1	NM_025236.4	ENSP00000244360.7
RNF39	ENST00000376751.8	c.403T>G	p.Ser135Ala	missense_variant	3/5	1		ENSP00000365942.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0037	.;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.21	N
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.10	N;N
REVEL	Benign	0.047
Sift	Benign	0.059	T;T
Sift4G	Uncertain	0.052	T;T
Polyphen		0.0030	B;B
Vest4		0.092
MutPred		0.23		Loss of glycosylation at S203 (P = 0.0118);Loss of glycosylation at S203 (P = 0.0118);
MVP		0.030
MPC		0.0027
ClinPred		0.049	T
GERP RS		4.0
Varity_R		0.065
gMVP		0.13

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: rs2074479; hg19: chr6-30041009;