Genetic Variant RNF214:p.Gln42Arg (chr11-117238618-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207343.4(RNF214):c.125A>G(p.Gln42Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,460,932 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

RNF214
NM_207343.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.62

Variant links:

Genes affected

RNF214 (HGNC:25335): (ring finger protein 214) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in protein ubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

RNF214 links:

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ACMG classification

Classification made for transcript

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=0.09179509).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF214	NM_207343.4 link	c.125A>G	p.Gln42Arg	missense_variant	Exon 3 of 15	ENST00000300650.9	NP_997226.2	Q8ND24-1A0A024R3D4
RNF214	NM_001077239.2 link	c.125A>G	p.Gln42Arg	missense_variant	Exon 3 of 15		NP_001070707.1	Q8ND24-1A0A024R3D4
RNF214	NM_001278249.2 link	c.125A>G	p.Gln42Arg	missense_variant	Exon 3 of 15		NP_001265178.1	Q8ND24-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF214	ENST00000300650.9 link	c.125A>G	p.Gln42Arg	missense_variant	Exon 3 of 15	1	NM_207343.4	ENSP00000300650.4		Q8ND24-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000522

AC:

AN:

249090

Hom.:

AF XY:

0.0000592

AC XY:

AN XY:

135166

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.000360

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1460932

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

726662

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000302

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.125A>G (p.Q42R) alteration is located in exon 3 (coding exon 2) of the RNF214 gene. This alteration results from a A to G substitution at nucleotide position 125, causing the glutamine (Q) at amino acid position 42 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.067

T;T;.;T;.

Eigen

Benign

-0.059

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.77

T;T;T;.;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.092

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

.;L;L;L;.

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.3

D;N;N;N;N

REVEL

Benign

0.068

Sift

Benign

0.033

D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;T;D;T

Polyphen

0.14

.;B;.;B;.

Vest4

0.41, 0.47, 0.50

MutPred

0.059

Loss of ubiquitination at K45 (P = 0.0157);Loss of ubiquitination at K45 (P = 0.0157);Loss of ubiquitination at K45 (P = 0.0157);Loss of ubiquitination at K45 (P = 0.0157);Loss of ubiquitination at K45 (P = 0.0157);

MVP

0.19

MPC

0.050

ClinPred

0.067

GERP RS

5.6

Varity_R

0.082

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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