7-5622942-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BS1_Supporting
The NM_207111.4(RNF216):āc.2690A>Gā(p.Asn897Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000378 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 32)
Exomes š: 0.000039 ( 0 hom. )
Consequence
RNF216
NM_207111.4 missense
NM_207111.4 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 5.35
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]
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ACMG classification
Classification made for transcript
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=0.37168136).
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000039 (57/1461662) while in subpopulation SAS AF= 0.0000464 (4/86254). AF 95% confidence interval is 0.00003. There are 0 homozygotes in gnomad4_exome. There are 25 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNF216 | NM_207111.4 | c.2690A>G | p.Asn897Ser | missense_variant | 17/17 | ENST00000389902.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNF216 | ENST00000389902.8 | c.2690A>G | p.Asn897Ser | missense_variant | 17/17 | 1 | NM_207111.4 | P4 | |
RNF216 | ENST00000425013.6 | c.2519A>G | p.Asn840Ser | missense_variant | 17/17 | 1 | A1 | ||
RNF216 | ENST00000389900.8 | c.*1807A>G | 3_prime_UTR_variant, NMD_transcript_variant | 16/16 | 1 | ||||
RNF216 | ENST00000469375.1 | n.907A>G | non_coding_transcript_exon_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152194Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251198Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135738
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GnomAD4 exome AF: 0.0000390 AC: 57AN: 1461662Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25AN XY: 727112
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152312Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74484
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 17, 2023 | The c.2690A>G (p.N897S) alteration is located in exon 17 (coding exon 16) of the RNF216 gene. This alteration results from a A to G substitution at nucleotide position 2690, causing the asparagine (N) at amino acid position 897 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of catalytic residue at N840 (P = 0.0766);.;
MVP
MPC
0.20
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at