rs773785078

Variant names:

• chr17-80372694-C-G
• rs773785078
• NM_001256071.3:c.12711C>G
• RNF213 p.Asp4237Glu

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001256071.3(RNF213):​c.12711C>G​(p.Asp4237Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: RNF213 NM_001256071.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.901
• Publications: 2 publications found

Genes affected

RNF213 (HGNC:14539): (ring finger protein 213) This gene encodes a protein containing a C3HC4-type RING finger domain, which is a specialized type of Zn-finger that binds two atoms of zinc and is thought to be involved in mediating protein-protein interactions. The protein also contains an AAA domain, which is associated with ATPase activity. This gene is a susceptibility gene for Moyamoya disease, a vascular disorder of intracranial arteries. This gene is also a translocation partner in anaplastic large cell lymphoma and inflammatory myofibroblastic tumor cases, where a t(2;17)(p23;q25) translocation has been identified with the anaplastic lymphoma kinase (ALK) gene on chromosome 2, and a t(8;17)(q24;q25) translocation has been identified with the MYC gene on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]

RNF213-AS1 (HGNC:54402): (RNF213 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3322472).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256071.3. 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
	RNF213	NM_001256071.3	MANE Select	c.12711C>G	p.Asp4237Glu	missense	Exon 48 of 68	NP_001243000.2	A0A0A0MTR7
	RNF213	NM_001410195.1		c.12858C>G	p.Asp4286Glu	missense	Exon 49 of 69	NP_001397124.1	A0A0A0MTC1
	RNF213	NM_020914.5		c.12858C>G	p.Asp4286Glu	missense	Exon 49 of 69	NP_065965.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF213	ENST00000582970.6	TSL:1 MANE Select	c.12711C>G	p.Asp4237Glu	missense	Exon 48 of 68	ENSP00000464087.1	A0A0A0MTR7
	RNF213	ENST00000508628.6	TSL:5	c.12858C>G	p.Asp4286Glu	missense	Exon 49 of 69	ENSP00000425956.2	A0A0A0MTC1
	RNF213	ENST00000411702.7	TSL:2	n.509C>G		non_coding_transcript_exon	Exon 2 of 21

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250764 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461580 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727098

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000671 AC: 3 AN: 44718

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: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Moyamoya disease 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Uncertain	0.97
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.075
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.90
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.087
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.0070	D
PromoterAI		-0.0033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=94/6	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs773785078;

hg19: chr17-78346494;