chr11-117234313-C-T

Variant names:

• chr11-117234313-C-T
• rs191545890
• NM_207343.4:c.41C>T

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.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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P14R) has been classified as Uncertain significance.

• 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
• 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=0.101854235).

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.41C>T	p.Pro14Leu	missense	Exon 2 of 15	NP_997226.2	Q8ND24-1
	RNF214	NM_001077239.2		c.41C>T	p.Pro14Leu	missense	Exon 2 of 15	NP_001070707.1	Q8ND24-1
	RNF214	NM_001278249.2		c.41C>T	p.Pro14Leu	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.41C>T	p.Pro14Leu	missense	Exon 2 of 15	ENSP00000300650.4	Q8ND24-1
	RNF214	ENST00000531452.5	TSL:1	c.41C>T	p.Pro14Leu	missense	Exon 2 of 15	ENSP00000431643.1	Q8ND24-1
	RNF214	ENST00000852075.1		c.41C>T	p.Pro14Leu	missense	Exon 2 of 15	ENSP00000522134.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.046	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.46	N
PhyloP100		2.0
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.26
MutPred		0.075		Loss of sheet (P = 0.0181)
MVP		0.20
MPC		0.091
ClinPred		0.82	D
GERP RS		3.9
PromoterAI		0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.13
gMVP		0.18
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs191545890; hg19: chr11-117105029;