chr6-30071184-C-T

Position:

• chr6-30071184-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_025236.4(RNF39):​c.986G>A​(p.Gly329Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000073 in 1,369,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: RNF39 NM_025236.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.19

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40146303).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF39	NM_025236.4	c.986G>A	p.Gly329Glu	missense_variant	4/4	ENST00000244360.8
RNF39	NM_170769.3	c.788G>A	p.Gly263Glu	missense_variant	5/5
RNF39	XM_017011325.2	c.731G>A	p.Gly244Glu	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF39	ENST00000244360.8	c.986G>A	p.Gly329Glu	missense_variant	4/4	1	NM_025236.4	P1
RNF39	ENST00000376751.8	c.788G>A	p.Gly263Glu	missense_variant	5/5	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.30e-7 AC: 1 AN: 1369122 Hom.: 0 Cov.: 30 AF XY: 0.00000149 AC XY: 1 AN XY: 671518

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: 0.00

Gnomad4 OTH exome AF: 0.0000178

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 27, 2022

The c.1190G>A (p.G397E) alteration is located in exon 4 (coding exon 4) of the RNF39 gene. This alteration results from a G to A substitution at nucleotide position 1190, causing the glycine (G) at amino acid position 397 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	.;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.11	N
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	.;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.9	N;D
REVEL	Uncertain	0.40
Sift	Benign	0.052	T;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.99	D;B
Vest4		0.34
MutPred		0.77		.;Gain of solvent accessibility (P = 0.0246);
MVP		0.49
MPC		2.5
ClinPred		0.66	D
GERP RS		4.3
Varity_R		0.15
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: chr6-30038961;