chr6-30073175-T-C

Position:

• chr6-30073175-T-C

Variant summary

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

The NM_025236.4(RNF39):​c.460A>G​(p.Met154Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF39 NM_025236.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.70

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=0.3730416).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF39	NM_025236.4	c.460A>G	p.Met154Val	missense_variant	3/4	ENST00000244360.8
RNF39	NM_170769.3	c.460A>G	p.Met154Val	missense_variant	3/5
RNF39	XM_017011325.2	c.205A>G	p.Met69Val	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF39	ENST00000244360.8	c.460A>G	p.Met154Val	missense_variant	3/4	1	NM_025236.4	P1
RNF39	ENST00000376751.8	c.460A>G	p.Met154Val	missense_variant	3/5	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Jan 02, 2024

The c.664A>G (p.M222V) alteration is located in exon 3 (coding exon 3) of the RNF39 gene. This alteration results from a A to G substitution at nucleotide position 664, causing the methionine (M) at amino acid position 222 to be replaced by a valine (V). 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	Pathogenic	0.57
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0058	.;T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.79	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.5	L;L
MutationTaster	Benign	0.95	N;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.23
Sift	Benign	0.093	T;T
Sift4G	Uncertain	0.018	D;D
Polyphen		0.95	P;B
Vest4		0.64
MutPred		0.36		Gain of methylation at K221 (P = 0.0172);Gain of methylation at K221 (P = 0.0172);
MVP		0.43
MPC		0.0039
ClinPred		0.45	T
GERP RS		4.0
Varity_R		0.32
gMVP		0.33

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: chr6-30040952;