Genetic Variant RNF39:p.Phe199Phe (chr6-30071573-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_025236.4(RNF39):c.597C>T(p.Phe199Phe) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RNF39
NM_025236.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.161

Variant links:

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]

RNF39 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP7

Synonymous conserved (PhyloP=-0.161 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF39	NM_025236.4 link	c.597C>T	p.Phe199Phe	synonymous_variant	Exon 4 of 4	ENST00000244360.8	NP_079512.3	Q9H2S5Q96QB5
RNF39	NM_170769.3 link	c.597C>T	p.Phe199Phe	synonymous_variant	Exon 4 of 5		NP_739575.3	Q9H2S5A0A1U9X8G2
RNF39	XM_017011325.2 link	c.342C>T	p.Phe114Phe	synonymous_variant	Exon 3 of 3		XP_016866814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF39	ENST00000244360.8 link	c.597C>T	p.Phe199Phe	synonymous_variant	Exon 4 of 4	1	NM_025236.4	ENSP00000244360.7		Q9H2S5
RNF39	ENST00000376751.8 link	c.597C>T	p.Phe199Phe	synonymous_variant	Exon 4 of 5	1		ENSP00000365942.4		Q9H2S5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1337458

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

657836

African (AFR)

AF:

0.00

AC:

AN:

28552

American (AMR)

AF:

0.00

AC:

AN:

27114

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22250

East Asian (EAS)

AF:

0.00

AC:

AN:

33926

South Asian (SAS)

AF:

0.00

AC:

AN:

73376

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33840

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5212

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1057550

Other (OTH)

AF:

0.00

AC:

AN:

55638

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.3

(source)

DANN

Benign

0.92

Mutation Taster

=100/0

polymorphism

(source)

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over