7-5622968-CAC-AAG

Variant names:

• chr7-5622968-CAC-AAG
• NM_207111.4:c.2662_2664delGTGinsCTT
• RNF216 p.Val888Leu

Variant summary

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

The NM_207111.4(RNF216):​c.2662_2664delGTGinsCTT​(p.Val888Leu) variant causes a missense change. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V888E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF216 NM_207111.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.27
• Publications: 0 publications found

Genes affected

RNF216 (HGNC:21698): (ring finger protein 216) This gene encodes a cytoplasmic protein which specifically colocalizes and interacts with the serine/threonine protein kinase, receptor-interacting protein (RIP). Zinc finger domains of the encoded protein are required for its interaction with RIP and for inhibition of TNF- and IL1-induced NF-kappa B activation pathways. The encoded protein may also function as an E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes and transfers it to substrates. Several alternatively spliced transcript variants have been described for this locus but the full-length natures of only some are known. [provided by RefSeq, Jul 2008]

RNF216 Gene-Disease associations (from GenCC):

• cerebellar ataxia-hypogonadism syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207111.4. 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
	RNF216	NM_207111.4	MANE Select	c.2662_2664delGTGinsCTT	p.Val888Leu	missense	N/A	NP_996994.1	Q9NWF9-1
	RNF216	NM_001377156.1		c.2491_2493delGTGinsCTT	p.Val831Leu	missense	N/A	NP_001364085.1	Q9NWF9-2
	RNF216	NM_207116.3		c.2491_2493delGTGinsCTT	p.Val831Leu	missense	N/A	NP_996999.1	Q9NWF9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF216	ENST00000389902.8	TSL:1 MANE Select	c.2662_2664delGTGinsCTT	p.Val888Leu	missense	N/A	ENSP00000374552.3	Q9NWF9-1
	RNF216	ENST00000425013.6	TSL:1	c.2491_2493delGTGinsCTT	p.Val831Leu	missense	N/A	ENSP00000404602.2	Q9NWF9-2
	RNF216	ENST00000389900.8	TSL:1	n.*1779_*1781delGTGinsCTT		non_coding_transcript_exon	Exon 16 of 16	ENSP00000374550.4	F8W6D1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.3

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: chr7-5662599;