11-117234313-C-T

Variant names:

• chr11-117234313-C-T
• NM_207343.4:c.41C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207343.4(RNF214):​c.41C>T​(p.Pro14Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RNF214 NM_207343.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02

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=0.101854235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF214	NM_207343.4	c.41C>T	p.Pro14Leu	missense_variant	Exon 2 of 15	ENST00000300650.9	NP_997226.2
RNF214	NM_001077239.2	c.41C>T	p.Pro14Leu	missense_variant	Exon 2 of 15		NP_001070707.1
RNF214	NM_001278249.2	c.41C>T	p.Pro14Leu	missense_variant	Exon 2 of 15		NP_001265178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF214	ENST00000300650.9	c.41C>T	p.Pro14Leu	missense_variant	Exon 2 of 15	1	NM_207343.4	ENSP00000300650.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461866 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	T;T;.;T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.046	N
LIST_S2	Uncertain	0.89	D;D;D;.;D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.10	T;T;T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.46	.;N;N;N;.
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.7	D;N;N;N;N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	.;D;.;D;.
Vest4		0.26, 0.26, 0.27, 0.31
MutPred		0.075		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP		0.20
MPC		0.091
ClinPred		0.82	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.13
gMVP		0.18

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: chr11-117105029;