11-117281395-G-T

Variant names:

• chr11-117281395-G-T
• rs377379346
• NM_207343.4:c.1227G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_207343.4(RNF214):​c.1227G>T​(p.Lys409Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000391 in 1,610,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: RNF214 NM_207343.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.945
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034347713).

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.1227G>T	p.Lys409Asn	missense	Exon 9 of 15	NP_997226.2	Q8ND24-1
	RNF214	NM_001077239.2		c.1227G>T	p.Lys409Asn	missense	Exon 9 of 15	NP_001070707.1	Q8ND24-1
	RNF214	NM_001278249.2		c.762G>T	p.Lys254Asn	missense	Exon 9 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.1227G>T	p.Lys409Asn	missense	Exon 9 of 15	ENSP00000300650.4	Q8ND24-1
	RNF214	ENST00000531452.5	TSL:1	c.1227G>T	p.Lys409Asn	missense	Exon 9 of 15	ENSP00000431643.1	Q8ND24-1
	RNF214	ENST00000852075.1		c.1227G>T	p.Lys409Asn	missense	Exon 9 of 15	ENSP00000522134.1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152004 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000962 AC: 24 AN: 249464 AF XY: 0.0000739

Gnomad AFR exome AF: 0.000387

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000835

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000281 AC: 41 AN: 1458170 Hom.: 0 Cov.: 29 AF XY: 0.0000289 AC XY: 21 AN XY: 725752

African (AFR) AF: 0.000269 AC: 9 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39680

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108656

Other (OTH) AF: 0.000282 AC: 17 AN: 60280

GnomAD4 genome AF: 0.000145 AC: 22 AN: 152122 Hom.: 0 Cov.: 30 AF XY: 0.000108 AC XY: 8 AN XY: 74340

African (AFR) AF: 0.000458 AC: 19 AN: 41512

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000582 AC: 3 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000350 Hom.: 0

Bravo AF: 0.000113

ExAC AF: 0.000107 AC: 13

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.092
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.94
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.042
Sift	Uncertain	0.014	D
Sift4G	Benign	0.17	T
Polyphen		0.59	P
Vest4		0.18
MutPred		0.32		Gain of ubiquitination at K408 (P = 0.0982)
MVP		0.22
MPC		0.89
ClinPred		0.033	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.67
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs377379346; hg19: chr11-117152111;