11-117238645-G-A

Variant names:

• chr11-117238645-G-A
• NM_207343.4:c.152G>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.152G>A​(p.Ser51Asn) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF214 NM_207343.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58

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=0.1680133).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF214	NM_207343.4	c.152G>A	p.Ser51Asn	missense_variant	Exon 3 of 15	ENST00000300650.9	NP_997226.2
RNF214	NM_001077239.2	c.152G>A	p.Ser51Asn	missense_variant	Exon 3 of 15		NP_001070707.1
RNF214	NM_001278249.2	c.152G>A	p.Ser51Asn	missense_variant, splice_region_variant	Exon 3 of 15		NP_001265178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF214	ENST00000300650.9	c.152G>A	p.Ser51Asn	missense_variant	Exon 3 of 15	1	NM_207343.4	ENSP00000300650.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.152G>A (p.S51N) alteration is located in exon 3 (coding exon 2) of the RNF214 gene. This alteration results from a G to A substitution at nucleotide position 152, causing the serine (S) at amino acid position 51 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	Benign	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.057	T;T;.;T;.
Eigen	Benign	-0.064
Eigen_PC	Benign	0.042
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.73	T;T;T;.;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.81	.;L;L;L;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.1	N;N;N;N;N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Pathogenic	0.0	D;T;T;T;T
Polyphen		0.56	.;P;.;P;.
Vest4		0.41, 0.41, 0.42, 0.50
MutPred		0.17		Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);
MVP		0.082
MPC		0.25
ClinPred		0.53	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr11-117109361;