rs2301753

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-30071463-G-A
• chr6-30071463-G-C
• chr6-30071463-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025236.4(RNF39):​c.707C>T​(p.Ala236Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,404,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RNF39 NM_025236.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05950302).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF39	NM_025236.4	c.707C>T	p.Ala236Val	missense_variant	Exon 4 of 4	ENST00000244360.8	NP_079512.3
RNF39	NM_170769.3	c.707C>T	p.Ala236Val	missense_variant	Exon 4 of 5		NP_739575.3
RNF39	XM_017011325.2	c.452C>T	p.Ala151Val	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>T	p.Ala236Val	missense_variant	Exon 4 of 4	1	NM_025236.4	ENSP00000244360.7
RNF39	ENST00000376751.8	c.707C>T	p.Ala236Val	missense_variant	Exon 4 of 5	1		ENSP00000365942.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1404838 Hom.: 0 Cov.: 32 AF XY: 0.00000287 AC XY: 2 AN XY: 697416

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000275

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.00071	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.053	N
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.11	N;N
REVEL	Benign	0.12
Sift	Benign	0.32	T;T
Sift4G	Benign	0.23	T;T
Polyphen		0.0080	B;B
Vest4		0.045
MutPred		0.21		Loss of glycosylation at S309 (P = 0.1859);Loss of glycosylation at S309 (P = 0.1859);
MVP		0.16
MPC		1.2
ClinPred		0.57	D
GERP RS		4.5
Varity_R		0.023
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-30039240;