chr7-5622876-G-T

Variant names:

• chr7-5622876-G-T
• NM_207111.4:c.2756C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207111.4(RNF216):​c.2756C>A​(p.Pro919Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,450,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P919P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RNF216 NM_207111.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.97

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2453154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF216	NM_207111.4	c.2756C>A	p.Pro919Gln	missense_variant	Exon 17 of 17	ENST00000389902.8	NP_996994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF216	ENST00000389902.8	c.2756C>A	p.Pro919Gln	missense_variant	Exon 17 of 17	1	NM_207111.4	ENSP00000374552.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1450296 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 719040

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.06e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.0040	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.045	T;.
Eigen	Benign	0.0091
Eigen_PC	Benign	0.080
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.68	N;N
REVEL	Benign	0.18
Sift	Benign	0.073	T;T
Sift4G	Uncertain	0.010	D;D
Polyphen		0.25	B;B
Vest4		0.52
MutPred		0.18		Loss of methylation at R865 (P = 0.0455);.;
MVP		0.62
MPC		0.20
ClinPred		0.76	D
GERP RS		4.0
Varity_R		0.076
gMVP		0.44

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-5662507;