chr6-30071560-C-G

Position:

• chr6-30071560-C-G

Variant summary

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

The NM_025236.4(RNF39):​c.610G>C​(p.Ala204Pro) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNF39 NM_025236.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.133

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=0.33904362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF39	NM_025236.4	c.610G>C	p.Ala204Pro	missense_variant	4/4	ENST00000244360.8
RNF39	NM_170769.3	c.610G>C	p.Ala204Pro	missense_variant	4/5
RNF39	XM_017011325.2	c.355G>C	p.Ala119Pro	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF39	ENST00000244360.8	c.610G>C	p.Ala204Pro	missense_variant	4/4	1	NM_025236.4	P1
RNF39	ENST00000376751.8	c.610G>C	p.Ala204Pro	missense_variant	4/5	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Jan 03, 2024

The c.814G>C (p.A272P) alteration is located in exon 4 (coding exon 4) of the RNF39 gene. This alteration results from a G to C substitution at nucleotide position 814, causing the alanine (A) at amino acid position 272 to be replaced by a proline (P). 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	0.93
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	.;T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.029
FATHMM_MKL	Benign	0.13	N
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.5	D;N
REVEL	Benign	0.14
Sift	Benign	0.20	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.99	D;D
Vest4		0.45
MutPred		0.52		Gain of disorder (P = 0.0926);Gain of disorder (P = 0.0926);
MVP		0.13
MPC		2.6
ClinPred		0.90	D
GERP RS		4.7
Varity_R		0.61
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr6-30039337;