14-24147787-C-G

Position:

• chr14-24147787-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017999.5(RNF31):​c.89C>G​(p.Ser30Cys) variant causes a missense change. 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 (★). Synonymous variant affecting the same amino acid position (i.e. S30S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNF31 NM_017999.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.80

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20302019).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF31	NM_017999.5	c.89C>G	p.Ser30Cys	missense_variant	1/21	ENST00000324103.11
RNF31	NM_001310332.2	c.-325-189C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF31	ENST00000324103.11	c.89C>G	p.Ser30Cys	missense_variant	1/21	1	NM_017999.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Jul 16, 2023

An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 30 of the RNF31 protein (p.Ser30Cys). 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. 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	0.094
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	.;.;T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Benign	0.64	D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	.;.;N
MutationTaster	Benign	0.67	D;D
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-4.3	D;N;N
REVEL	Benign	0.095
Sift	Uncertain	0.022	D;D;D
Sift4G	Uncertain	0.014	D;D;D
Polyphen		0.70	.;.;P
Vest4		0.31
MutPred		0.34		Gain of catalytic residue at L31 (P = 2e-04);Gain of catalytic residue at L31 (P = 2e-04);Gain of catalytic residue at L31 (P = 2e-04);
MVP		0.39
MPC		0.48
ClinPred		0.89	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.22
gMVP		0.28

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

Other links and lift over

dbSNP: rs937595683; hg19: chr14-24616996;