11-117279941-G-C

Position:

• chr11-117279941-G-C

Variant summary

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

The NM_207343.4(RNF214):​c.993G>C​(p.Lys331Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF214 NM_207343.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.85

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF214	NM_207343.4	c.993G>C	p.Lys331Asn	missense_variant	7/15	ENST00000300650.9	NP_997226.2
RNF214	NM_001077239.2	c.993G>C	p.Lys331Asn	missense_variant	7/15		NP_001070707.1
RNF214	NM_001278249.2	c.528G>C	p.Lys176Asn	missense_variant	7/15		NP_001265178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF214	ENST00000300650.9	c.993G>C	p.Lys331Asn	missense_variant	7/15	1	NM_207343.4	ENSP00000300650	P3
RNF214	ENST00000531452.5	c.993G>C	p.Lys331Asn	missense_variant	7/15	1		ENSP00000431643	P3
RNF214	ENST00000531287.5	c.528G>C	p.Lys176Asn	missense_variant	7/15	2		ENSP00000435361	A1
RNF214	ENST00000530849.1	c.528G>C	p.Lys176Asn	missense_variant	6/13	5		ENSP00000432903

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Apr 17, 2023

The c.993G>C (p.K331N) alteration is located in exon 7 (coding exon 6) of the RNF214 gene. This alteration results from a G to C substitution at nucleotide position 993, causing the lysine (K) at amino acid position 331 to be replaced by an asparagine (N). 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	0.95
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T;.;T;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	D;D;.;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.56	D;D;D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.69	N;.;N;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.021	D;D;D;D
Sift4G	Uncertain	0.027	D;D;D;D
Polyphen		1.0	D;.;D;.
Vest4		0.73
MutPred		0.45		Loss of ubiquitination at K331 (P = 0.003);.;Loss of ubiquitination at K331 (P = 0.003);.;
MVP		0.13
MPC		0.34
ClinPred		0.93	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.72

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: chr11-117150657;