chr11-117246941-G-C

Position:

• chr11-117246941-G-C

Variant summary

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

The NM_207343.4(RNF214):​c.952G>C​(p.Gly318Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 33)
• Consequence: RNF214 NM_207343.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.37

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=0.16994092).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF214	NM_207343.4	c.952G>C	p.Gly318Arg	missense_variant	6/15	ENST00000300650.9	NP_997226.2
RNF214	NM_001077239.2	c.952G>C	p.Gly318Arg	missense_variant	6/15		NP_001070707.1
RNF214	NM_001278249.2	c.487G>C	p.Gly163Arg	missense_variant	6/15		NP_001265178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF214	ENST00000300650.9	c.952G>C	p.Gly318Arg	missense_variant	6/15	1	NM_207343.4	ENSP00000300650	P3
RNF214	ENST00000531452.5	c.952G>C	p.Gly318Arg	missense_variant	6/15	1		ENSP00000431643	P3
RNF214	ENST00000531287.5	c.487G>C	p.Gly163Arg	missense_variant	6/15	2		ENSP00000435361	A1
RNF214	ENST00000530849.1	c.487G>C	p.Gly163Arg	missense_variant	5/13	5		ENSP00000432903

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

May 30, 2024

The c.952G>C (p.G318R) alteration is located in exon 6 (coding exon 5) of the RNF214 gene. This alteration results from a G to C substitution at nucleotide position 952, causing the glycine (G) at amino acid position 318 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	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T;.;T;.
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.94	D;D;.;D
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	0.0	N;.;N;.
MutationTaster	Benign	0.69	D;D;N;N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Benign	0.30	T;T;T;T
Polyphen		0.96	D;.;D;.
Vest4		0.37
MutPred		0.39		Gain of helix (P = 0.027);.;Gain of helix (P = 0.027);.;
MVP		0.18
MPC		0.30
ClinPred		0.70	D
GERP RS		3.8
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.12
gMVP		0.47

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: chr11-117117657;