Variant 11-117246927-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_207343.4(RNF214):c.938A>C(p.Lys313Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,996 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 6.9e-7 ( 0 hom. )

Consequence

RNF214
NM_207343.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.61

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34032515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF214	NM_207343.4 link	c.938A>C	p.Lys313Thr	missense_variant	6/15	ENST00000300650.9	NP_997226.2	Q8ND24-1A0A024R3D4
RNF214	NM_001077239.2 link	c.938A>C	p.Lys313Thr	missense_variant	6/15		NP_001070707.1	Q8ND24-1A0A024R3D4
RNF214	NM_001278249.2 link	c.473A>C	p.Lys158Thr	missense_variant	6/15		NP_001265178.1	Q8ND24-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RNF214	ENST00000300650.9 link	c.938A>C	p.Lys313Thr	missense_variant	6/15	1	NM_207343.4	ENSP00000300650.4	Q8ND24-1
RNF214	ENST00000531452.5 link	c.938A>C	p.Lys313Thr	missense_variant	6/15	1		ENSP00000431643.1	Q8ND24-1
RNF214	ENST00000531287.5 link	c.473A>C	p.Lys158Thr	missense_variant	6/15	2		ENSP00000435361.1	Q8ND24-2
RNF214	ENST00000530849.1 link	c.473A>C	p.Lys158Thr	missense_variant	5/13	5		ENSP00000432903.1	E9PN76

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247634

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134550

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000296

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458996

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725938

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000227

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 10, 2024

The c.938A>C (p.K313T) alteration is located in exon 6 (coding exon 5) of the RNF214 gene. This alteration results from a A to C substitution at nucleotide position 938, causing the lysine (K) at amino acid position 313 to be replaced by a threonine (T). 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

Pathogenic

0.68

BayesDel_addAF

Uncertain

0.051

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;.;T;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.93

D;D;.;D

M_CAP

Benign

0.045

MetaRNN

Benign

0.34

T;T;T;T

MetaSVM

Uncertain

-0.10

MutationAssessor

Benign

0.34

N;.;N;.

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.3

D;D;D;D

REVEL

Benign

0.16

Sift

Benign

0.10

T;T;T;T

Sift4G

Uncertain

0.0080

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.55

MutPred

0.34

Loss of ubiquitination at K313 (P = 0.0116);.;Loss of ubiquitination at K313 (P = 0.0116);.;

MVP

0.34

MPC

0.33

ClinPred

0.87

GERP RS

5.9

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.12

gMVP

0.49

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