chr6-30075315-G-C

Position:

• chr6-30075315-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025236.4(RNF39):​c.271C>G​(p.Leu91Val) 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: 32)
• Consequence: RNF39 NM_025236.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF39	NM_025236.4	c.271C>G	p.Leu91Val	missense_variant	1/4	ENST00000244360.8
RNF39	NM_170769.3	c.271C>G	p.Leu91Val	missense_variant	1/5
RNF39	XM_017011325.2	c.39C>G	p.Ser13Arg	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF39	ENST00000244360.8	c.271C>G	p.Leu91Val	missense_variant	1/4	1	NM_025236.4	P1
RNF39	ENST00000376751.8	c.271C>G	p.Leu91Val	missense_variant	1/5	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Nov 09, 2021

The c.475C>G (p.L159V) alteration is located in exon 1 (coding exon 1) of the RNF39 gene. This alteration results from a C to G substitution at nucleotide position 475, causing the leucine (L) at amino acid position 159 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	Benign	0.31
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0056	.;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.38	N
M_CAP	Pathogenic	0.79	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.90	L;L
MutationTaster	Benign	0.94	D;D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.16
Sift	Uncertain	0.0060	D;T
Sift4G	Benign	0.28	T;T
Polyphen		0.98	D;D
Vest4		0.081
MutPred		0.32		Loss of loop (P = 0.0986);Loss of loop (P = 0.0986);
MVP		0.19
MPC		1.2
ClinPred		0.31	T
GERP RS		4.0
Varity_R		0.16
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: 1

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: chr6-30043092;