Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3PP5

The ENST00000324103.11(RNF31):c.215T>C(p.Leu72Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. L72L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

RNF31
ENST00000324103.11 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.94

Publications

13 publications found

Variant links:

Genes affected

RNF31 (HGNC:16031): (ring finger protein 31) The protein encoded by this gene contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-DNA and protein-protein interactions. The encoded protein is the E3 ubiquitin-protein ligase component of the linear ubiquitin chain assembly complex. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]

RNF31 Gene-Disease associations (from GenCC):

autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
immunodeficiency 115 with autoinflammation
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

RNF31 links:

ENSG00000259529 (HGNC:):

ENSG00000259529 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.777

PP5

Variant 14-24147998-T-C is Pathogenic according to our data. Variant chr14-24147998-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 203412.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000324103.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF31	NM_017999.5	MANE Select	c.215T>C	p.Leu72Pro	missense	Exon 2 of 21	NP_060469.4
	RNF31	NM_001310332.2		c.-303T>C		5_prime_UTR	Exon 2 of 21	NP_001297261.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RNF31	ENST00000324103.11	TSL:1 MANE Select	c.215T>C	p.Leu72Pro	missense	Exon 2 of 21	ENSP00000315112.6
ENSG00000259529	ENST00000558468.2	TSL:2	n.215T>C		non_coding_transcript_exon	Exon 2 of 29	ENSP00000457512.2
RNF31	ENST00000559275.5	TSL:1	c.-303T>C		5_prime_UTR	Exon 2 of 21	ENSP00000453574.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency 115 with autoinflammation (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.83

M_CAP

Benign

0.081

MetaRNN

Pathogenic

0.78

MetaSVM

Benign

-0.37

MutationAssessor

Benign

1.6

PhyloP100

6.9

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-5.5

REVEL

Uncertain

0.34

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.93

MutPred

0.65

Gain of loop (P = 0.002)

MVP

0.71

MPC

1.1

ClinPred

0.99

GERP RS

5.3

PromoterAI

-0.0042

Neutral

(source)

Varity_R

0.92

gMVP

0.94

Mutation Taster

=23/77

disease causing

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over