dbSNP rs2033238369: RNF214:p.Thr289Ala (chr11-117246854-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207343.4(RNF214):c.865A>G(p.Thr289Ala) 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RNF214
NM_207343.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07235831).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207343.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF214	NM_207343.4	MANE Select	c.865A>G	p.Thr289Ala	missense	Exon 6 of 15	NP_997226.2	Q8ND24-1
RNF214	NM_001077239.2		c.865A>G	p.Thr289Ala	missense	Exon 6 of 15	NP_001070707.1	Q8ND24-1
RNF214	NM_001278249.2		c.400A>G	p.Thr134Ala	missense	Exon 6 of 15	NP_001265178.1	Q8ND24-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF214	ENST00000300650.9	TSL:1 MANE Select	c.865A>G	p.Thr289Ala	missense	Exon 6 of 15	ENSP00000300650.4	Q8ND24-1
RNF214	ENST00000531452.5	TSL:1	c.865A>G	p.Thr289Ala	missense	Exon 6 of 15	ENSP00000431643.1	Q8ND24-1
RNF214	ENST00000852075.1		c.865A>G	p.Thr289Ala	missense	Exon 6 of 15	ENSP00000522134.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460664

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726626

African (AFR)

AF:

0.00

AC:

AN:

33436

American (AMR)

AF:

0.00

AC:

AN:

44610

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

86078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111432

Other (OTH)

AF:

0.00

AC:

AN:

60324

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Uncertain

0.030

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.043

Eigen

Benign

-0.12

Eigen_PC

Benign

0.031

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.69

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.072

MetaSVM

Uncertain

0.47

MutationAssessor

Benign

-0.34

PhyloP100

4.0

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.77

REVEL

Benign

0.074

Sift

Benign

0.40

Sift4G

Benign

0.44

Polyphen

0.39

Vest4

0.30

MutPred

0.21

Loss of phosphorylation at T289 (P = 0.0074)

MVP

0.043

MPC

0.14

ClinPred

0.73

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.033

gMVP

0.35

Mutation Taster

=78/22

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over