11-117238980-G-A

Variant names:

• chr11-117238980-G-A
• rs2032994296
• NM_207343.4:c.487G>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.487G>A​(p.Gly163Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RNF214 NM_207343.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.54

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=0.12653515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF214	NM_207343.4	c.487G>A	p.Gly163Ser	missense_variant	Exon 3 of 15	ENST00000300650.9	NP_997226.2
RNF214	NM_001077239.2	c.487G>A	p.Gly163Ser	missense_variant	Exon 3 of 15		NP_001070707.1
RNF214	NM_001278249.2	c.153+334G>A		intron_variant	Intron 3 of 14		NP_001265178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF214	ENST00000300650.9	c.487G>A	p.Gly163Ser	missense_variant	Exon 3 of 15	1	NM_207343.4	ENSP00000300650.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461882 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.487G>A (p.G163S) 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 487, causing the glycine (G) at amino acid position 163 to be replaced by a serine (S). 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	0.086
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T;.
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.81	L;L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.40	N;N
REVEL	Benign	0.14
Sift	Benign	0.062	T;T
Sift4G	Uncertain	0.035	D;D
Polyphen		1.0	D;D
Vest4		0.37
MutPred		0.16		Gain of phosphorylation at G163 (P = 0.0178);Gain of phosphorylation at G163 (P = 0.0178);
MVP		0.082
MPC		0.052
ClinPred		0.74	D
GERP RS		4.8
Varity_R		0.12
gMVP		0.23

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

LitVar

Other links and lift over

dbSNP: rs2032994296; hg19: chr11-117109696;