Variant 14-24147750-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017999.5(RNF31):c.52G>A(p.Ala18Thr) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RNF31
NM_017999.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.374

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 links:

ENSG00000259529 (HGNC:):

ENSG00000259529 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026993692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF31	NM_017999.5 link	c.52G>A	p.Ala18Thr	missense_variant	Exon 1 of 21	ENST00000324103.11	NP_060469.4
RNF31	NM_001310332.2 link	c.-325-226G>A		intron_variant	Intron 1 of 20		NP_001297261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF31	ENST00000324103.11 link	c.52G>A	p.Ala18Thr	missense_variant	Exon 1 of 21	1	NM_017999.5	ENSP00000315112.6		Q96EP0-1
ENSG00000259529	ENST00000558468.2 link	n.52G>A		non_coding_transcript_exon_variant	Exon 1 of 29	2		ENSP00000457512.2		A0A0B4J293

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1412714

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

699264

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000848

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jan 08, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 18 of the RNF31 protein (p.Ala18Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RNF31-related conditions. ClinVar contains an entry for this variant (Variation ID: 2971595). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

.;.;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.47

M_CAP

Benign

0.0049

MetaRNN

Benign

0.027

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

.;.;L

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.0

D;N;N

REVEL

Benign

0.083

Sift

Benign

0.10

T;T;T

Sift4G

Pathogenic

0.0

D;T;T

Polyphen

0.0

.;.;B

Vest4

0.057

MutPred

0.26

Gain of phosphorylation at A18 (P = 0.0398);Gain of phosphorylation at A18 (P = 0.0398);Gain of phosphorylation at A18 (P = 0.0398);

MVP

0.32

MPC

0.22

ClinPred

0.45

GERP RS

3.0

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.094

gMVP

0.21

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over