17-80369572-A-G

Variant names:

• chr17-80369572-A-G
• rs746280089
• NM_001256071.3:c.12226A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001256071.3(RNF213):​c.12226A>G​(p.Ile4076Val) 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 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 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: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RNF213 NM_001256071.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.343
• Publications: 6 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: 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=0.07508665).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF213	NM_001256071.3	MANE Select	c.12226A>G	p.Ile4076Val	missense	Exon 45 of 68	NP_001243000.2
	RNF213	NM_001410195.1		c.12373A>G	p.Ile4125Val	missense	Exon 46 of 69	NP_001397124.1
	RNF213	NM_020914.5		c.12373A>G	p.Ile4125Val	missense	Exon 46 of 69	NP_065965.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF213	ENST00000582970.6	TSL:1 MANE Select	c.12226A>G	p.Ile4076Val	missense	Exon 45 of 68	ENSP00000464087.1
	RNF213	ENST00000508628.6	TSL:5	c.12373A>G	p.Ile4125Val	missense	Exon 46 of 69	ENSP00000425956.2
	RNF213	ENST00000558116.5	TSL:2	n.1555A>G		non_coding_transcript_exon	Exon 11 of 23

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251488 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461888 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 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: 0.0000116 AC: 1 AN: 86258

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Moyamoya disease 2 Uncertain:1

Sep 08, 2014

Department of Internal Medicine, University of Texas Health Science Center at Houston

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.8
DANN	Benign	0.74
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.34
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.025
Sift	Benign	0.33	T
Sift4G	Benign	0.33	T
Vest4		0.17
MVP		0.23
MPC		0.12
ClinPred		0.028	T
GERP RS		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs746280089; hg19: chr17-78343372;