11-117239841-A-G

Position:

• chr11-117239841-A-G

Variant summary

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

The NM_207343.4(RNF214):​c.659A>G​(p.Gln220Arg) 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.65

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]

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=0.24194375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF214	NM_207343.4	c.659A>G	p.Gln220Arg	missense_variant	4/15	ENST00000300650.9
RNF214	NM_001077239.2	c.659A>G	p.Gln220Arg	missense_variant	4/15
RNF214	NM_001278249.2	c.194A>G	p.Gln65Arg	missense_variant	4/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF214	ENST00000300650.9	c.659A>G	p.Gln220Arg	missense_variant	4/15	1	NM_207343.4	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1402852 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 701458

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.659A>G (p.Q220R) alteration is located in exon 4 (coding exon 3) of the RNF214 gene. This alteration results from a A to G substitution at nucleotide position 659, causing the glutamine (Q) at amino acid position 220 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	0.14
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T;.;T;.
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.87	D;D;.;T
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Uncertain	0.68	D
MutationAssessor	Benign	0.81	L;.;L;.
MutationTaster	Benign	0.93	D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.5	N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.16	T;T;T;T
Sift4G	Uncertain	0.015	D;D;D;T
Polyphen		0.082	B;.;B;.
Vest4		0.41
MutPred		0.066		Gain of phosphorylation at T218 (P = 0.0991);.;Gain of phosphorylation at T218 (P = 0.0991);.;
MVP		0.66
MPC		0.11
ClinPred		0.72	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-117110557;