1-6206652-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_207396.3(RNF207):āc.117C>Gā(p.Asp39Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,607,970 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 33)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
RNF207
NM_207396.3 missense
NM_207396.3 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 2.60
Genes affected
RNF207 (HGNC:32947): (ring finger protein 207) Enables Hsp70 protein binding activity; chaperone binding activity; and transmembrane transporter binding activity. Involved in positive regulation of delayed rectifier potassium channel activity; positive regulation of gene expression; and positive regulation of voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
RPL22 (HGNC:10315): (ribosomal protein L22) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a cytoplasmic ribosomal protein that is a component of the 60S subunit. The protein belongs to the L22E family of ribosomal proteins. Its initiating methionine residue is post-translationally removed. The protein can bind specifically to Epstein-Barr virus-encoded RNAs (EBERs) 1 and 2. The mouse protein has been shown to be capable of binding to heparin. Transcript variants utilizing alternative polyA signals exist. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. It was previously thought that this gene mapped to 3q26 and that it was fused to the acute myeloid leukemia 1 (AML1) gene located at 21q22 in some therapy-related myelodysplastic syndrome patients with 3;21 translocations; however, these fusions actually involve a ribosomal protein L22 pseudogene located at 3q26, and this gene actually maps to 1p36.3-p36.2. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNF207 | NM_207396.3 | c.117C>G | p.Asp39Glu | missense_variant | 2/18 | ENST00000377939.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNF207 | ENST00000377939.5 | c.117C>G | p.Asp39Glu | missense_variant | 2/18 | 5 | NM_207396.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152250Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1455720Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2AN XY: 724504
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152250Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74384
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 23, 2023 | The c.117C>G (p.D39E) alteration is located in exon 2 (coding exon 1) of the RNF207 gene. This alteration results from a C to G substitution at nucleotide position 117, causing the aspartic acid (D) at amino acid position 39 to be replaced by a glutamic acid (E). 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
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
D
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of sheet (P = 0.1945);
MVP
MPC
ClinPred
D
GERP RS
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