11-117234331-C-A

Variant names:

• chr11-117234331-C-A
• NM_207343.4:c.59C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207343.4(RNF214):​c.59C>A​(p.Ser20Tyr) 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. 14/22 in silico tools predict 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: 3.38
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.122712165).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207343.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF214	NM_207343.4	MANE Select	c.59C>A	p.Ser20Tyr	missense	Exon 2 of 15	NP_997226.2	Q8ND24-1
	RNF214	NM_001077239.2		c.59C>A	p.Ser20Tyr	missense	Exon 2 of 15	NP_001070707.1	Q8ND24-1
	RNF214	NM_001278249.2		c.59C>A	p.Ser20Tyr	missense	Exon 2 of 15	NP_001265178.1	Q8ND24-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF214	ENST00000300650.9	TSL:1 MANE Select	c.59C>A	p.Ser20Tyr	missense	Exon 2 of 15	ENSP00000300650.4	Q8ND24-1
	RNF214	ENST00000531452.5	TSL:1	c.59C>A	p.Ser20Tyr	missense	Exon 2 of 15	ENSP00000431643.1	Q8ND24-1
	RNF214	ENST00000852075.1		c.59C>A	p.Ser20Tyr	missense	Exon 2 of 15	ENSP00000522134.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.071	T
Eigen	Benign	0.059
Eigen_PC	Benign	0.057
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.81	L
PhyloP100		3.4
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.28		Gain of catalytic residue at S20 (P = 0.0031)
MVP		0.12
MPC		0.35
ClinPred		0.94	D
GERP RS		4.6
PromoterAI		0.0039	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.32
gMVP		0.37
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr11-117105047;