Variant 11-117239109-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_207343.4(RNF214):c.616C>A(p.Gln206Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,604,090 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RNF214
NM_207343.4 missense, splice_region

Scores

Splicing: ADA: 0.2275

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RNF214	NM_207343.4 linkuse as main transcript	c.616C>A	p.Gln206Lys	missense_variant, splice_region_variant	3/15	ENST00000300650.9
RNF214	NM_001077239.2 linkuse as main transcript	c.616C>A	p.Gln206Lys	missense_variant, splice_region_variant	3/15
RNF214	NM_001278249.2 linkuse as main transcript	c.153+463C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF214	ENST00000300650.9 linkuse as main transcript	c.616C>A	p.Gln206Lys	missense_variant, splice_region_variant	3/15	1	NM_207343.4	P3	Q8ND24-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1451950

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721092

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Jan 24, 2024

The c.616C>A (p.Q206K) alteration is located in exon 3 (coding exon 2) of the RNF214 gene. This alteration results from a C to A substitution at nucleotide position 616, causing the glutamine (Q) at amino acid position 206 to be replaced by a lysine (K). 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

0.83

BayesDel_addAF

Uncertain

0.077

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

T;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.78

T;.

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.46

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;L

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.079

Sift

Uncertain

0.0020

D;D

Sift4G

Benign

0.18

T;T

Polyphen

0.79

P;P

Vest4

0.71

MutPred

0.30

Gain of ubiquitination at Q206 (P = 0.0029);Gain of ubiquitination at Q206 (P = 0.0029);

MVP

0.28

MPC

0.055

ClinPred

0.62

GERP RS

5.0

Varity_R

0.32

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.23

dbscSNV1_RF

Benign

0.29

SpliceAI score (max)

0.030

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