6-30075608-G-T

Position:

• chr6-30075608-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.-23C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,104 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RNF39 NM_025236.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.364

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=0.04617521).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF39	NM_025236.4	c.-23C>A		5_prime_UTR_variant	1/4	ENST00000244360.8
RNF39	NM_170769.3	c.-23C>A		5_prime_UTR_variant	1/5
RNF39	XM_017011325.2	c.-255C>A		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF39	ENST00000244360.8	c.-23C>A		5_prime_UTR_variant	1/4	1	NM_025236.4	P1
RNF39	ENST00000376751.8	c.-23C>A		5_prime_UTR_variant	1/5	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456104 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 724624

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Apr 22, 2022

The c.182C>A (p.A61E) alteration is located in exon 1 (coding exon 1) of the RNF39 gene. This alteration results from a C to A substitution at nucleotide position 182, causing the alanine (A) at amino acid position 61 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	0.090
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Benign	0.93
DEOGEN2	Benign	0.0012	.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.024	N
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.046	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.47	N;N
REVEL	Benign	0.043
Sift	Uncertain	0.0090	D;D
Sift4G	Benign	0.32	T;T
Polyphen		0.16	B;B
Vest4		0.085
MutPred		0.25		Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);
MVP		0.040
MPC		1.0
ClinPred		0.093	T
GERP RS		-7.3
Varity_R		0.076
gMVP		0.18

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: chr6-30043385;