chr17-80367978-GC-AT

Variant names:

• chr17-80367978-GC-AT
• NM_001256071.3:c.11990_11991delGCinsAT
• RNF213 p.Cys3997Tyr

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001256071.3(RNF213):​c.11990_11991delGCinsAT​(p.Cys3997Tyr) variant causes a missense 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 MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. C3997C) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNF213 NM_001256071.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.84
• 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 1 ACMG points.

• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF213	NM_001256071.3	MANE Select	c.11990_11991delGCinsAT	p.Cys3997Tyr	missense	N/A	NP_001243000.2	A0A0A0MTR7
	RNF213	NM_001410195.1		c.12137_12138delGCinsAT	p.Cys4046Tyr	missense	N/A	NP_001397124.1	A0A0A0MTC1
	RNF213	NM_020914.5		c.12137_12138delGCinsAT	p.Cys4046Tyr	missense	N/A	NP_065965.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF213	ENST00000582970.6	TSL:1 MANE Select	c.11990_11991delGCinsAT	p.Cys3997Tyr	missense	N/A	ENSP00000464087.1	A0A0A0MTR7
	RNF213	ENST00000508628.6	TSL:5	c.12137_12138delGCinsAT	p.Cys4046Tyr	missense	N/A	ENSP00000425956.2	A0A0A0MTC1
	RNF213	ENST00000558116.5	TSL:2	n.1319_1320delGCinsAT		non_coding_transcript_exon	Exon 10 of 23

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.8

Splicing

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

hg19: chr17-78341778;