14-24147756-G-C

Variant names:

• chr14-24147756-G-C
• rs951102555
• NM_017999.5:c.58G>C

Variant summary

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

The NM_017999.5(RNF31):​c.58G>C​(p.Ala20Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNF31 NM_017999.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41

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]

ENSG00000259529 (HGNC:):

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=0.22705582).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF31	NM_017999.5	c.58G>C	p.Ala20Pro	missense_variant	Exon 1 of 21	ENST00000324103.11	NP_060469.4
RNF31	NM_001310332.2	c.-325-220G>C		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	c.58G>C	p.Ala20Pro	missense_variant	Exon 1 of 21	1	NM_017999.5	ENSP00000315112.6
ENSG00000259529	ENST00000558468.2	n.58G>C		non_coding_transcript_exon_variant	Exon 1 of 29	2		ENSP00000457512.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	.;.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.056
FATHMM_MKL	Benign	0.54	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	.;.;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.0	D;N;N
REVEL	Benign	0.18
Sift	Uncertain	0.0090	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.050	.;.;B
Vest4		0.35
MutPred		0.27		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.76
MPC		0.87
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.69
gMVP		0.67

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: rs951102555; hg19: chr14-24616965;