6-30071463-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025236.4(RNF39):​c.707C>G​(p.Ala236Gly) 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. 14/22 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RNF39 NM_025236.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.073426515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF39	NM_025236.4	c.707C>G	p.Ala236Gly	missense_variant	Exon 4 of 4	ENST00000244360.8	NP_079512.3
RNF39	NM_170769.3	c.707C>G	p.Ala236Gly	missense_variant	Exon 4 of 5		NP_739575.3
RNF39	XM_017011325.2	c.452C>G	p.Ala151Gly	missense_variant	Exon 3 of 3		XP_016866814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF39	ENST00000244360.8	c.707C>G	p.Ala236Gly	missense_variant	Exon 4 of 4	1	NM_025236.4	ENSP00000244360.7
RNF39	ENST00000376751.8	c.707C>G	p.Ala236Gly	missense_variant	Exon 4 of 5	1		ENSP00000365942.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1404848 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 697418

African (AFR) AF: 0.00 AC: 0 AN: 30306

American (AMR) AF: 0.00 AC: 0 AN: 37508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24266

East Asian (EAS) AF: 0.00 AC: 0 AN: 36290

South Asian (SAS) AF: 0.00 AC: 0 AN: 80470

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091510

Other (OTH) AF: 0.00 AC: 0 AN: 58116

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0024	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.10	N
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.073	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N
PhyloP100		1.5
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	0.040	N;N
REVEL	Benign	0.15
Sift	Benign	0.081	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.0020	B;B
Vest4		0.050
MutPred		0.20		Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);
MVP		0.18
MPC		1.3
ClinPred		0.36	T
GERP RS		4.5
Varity_R		0.029
gMVP		0.11
Mutation Taster		=99/1	polymorphism

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;