11-117234331-C-A

Position:

• chr11-117234331-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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

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=0.122712165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF214	NM_207343.4	c.59C>A	p.Ser20Tyr	missense_variant	2/15	ENST00000300650.9
RNF214	NM_001077239.2	c.59C>A	p.Ser20Tyr	missense_variant	2/15
RNF214	NM_001278249.2	c.59C>A	p.Ser20Tyr	missense_variant	2/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF214	ENST00000300650.9	c.59C>A	p.Ser20Tyr	missense_variant	2/15	1	NM_207343.4	P3

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

Jan 23, 2024

The c.59C>A (p.S20Y) alteration is located in exon 2 (coding exon 1) of the RNF214 gene. This alteration results from a C to A substitution at nucleotide position 59, causing the serine (S) at amino acid position 20 to be replaced by a tyrosine (Y). 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	0.15
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.071	T;T;.;T;.
Eigen	Benign	0.059
Eigen_PC	Benign	0.057
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.79	T;T;T;.;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-0.74	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-4.7	D;N;N;N;N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	.;D;.;D;.
Vest4		0.48, 0.55, 0.49, 0.58
MutPred		0.28		Gain of catalytic residue at S20 (P = 0.0031);Gain of catalytic residue at S20 (P = 0.0031);Gain of catalytic residue at S20 (P = 0.0031);Gain of catalytic residue at S20 (P = 0.0031);Gain of catalytic residue at S20 (P = 0.0031);
MVP		0.12
MPC		0.35
ClinPred		0.94	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.32
gMVP		0.37

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-117105047;