rs797045188

Variant names:

• chr17-80386817-G-GAGGGCAAACAGAGCGTGCAGC
• rs797045188
• NM_001256071.3:c.14850_14851insGGCAAACAGAGCGTGCAGCAG

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM4 PP3

The NM_001256071.3(RNF213):​c.14850_14851insGGCAAACAGAGCGTGCAGCAG​(p.Glu4950_Phe4951insGlyLysGlnSerValGlnGln) variant causes a conservative inframe insertion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (no stars). Synonymous variant affecting the same amino acid position (i.e. F4951F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF213 NM_001256071.3 conservative_inframe_insertion
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 8.75
• Publications: 0 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 3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001256071.3.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.14850_14851insGGCAAACAGAGCGTGCAGCAG	p.Glu4950_Phe4951insGlyLysGlnSerValGlnGln	conservative_inframe_insertion	Exon 63 of 68	NP_001243000.2
	RNF213	NM_001410195.1		c.14997_14998insGGCAAACAGAGCGTGCAGCAG	p.Glu4999_Phe5000insGlyLysGlnSerValGlnGln	conservative_inframe_insertion	Exon 64 of 69	NP_001397124.1
	RNF213	NM_020914.5		c.14997_14998insGGCAAACAGAGCGTGCAGCAG	p.Glu4999_Phe5000insGlyLysGlnSerValGlnGln	conservative_inframe_insertion	Exon 64 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.14850_14851insGGCAAACAGAGCGTGCAGCAG	p.Glu4950_Phe4951insGlyLysGlnSerValGlnGln	conservative_inframe_insertion	Exon 63 of 68	ENSP00000464087.1
	RNF213	ENST00000427003.7	TSL:1	n.964_965insGGCAAACAGAGCGTGCAGCAG		non_coding_transcript_exon	Exon 7 of 12
	RNF213	ENST00000508628.6	TSL:5	c.14997_14998insGGCAAACAGAGCGTGCAGCAG	p.Glu4999_Phe5000insGlyLysGlnSerValGlnGln	conservative_inframe_insertion	Exon 64 of 69	ENSP00000425956.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

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
PhyloP100		8.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs797045188; hg19: chr17-78360617;