chr22-20122264-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001278639.2(RANBP1):c.384G>C(p.Met128Ile) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000515 in 1,612,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000055 ( 0 hom. )
Consequence
RANBP1
NM_001278639.2 missense, splice_region
NM_001278639.2 missense, splice_region
Scores
3
4
11
Splicing: ADA: 0.9994
2
Clinical Significance
Conservation
PhyloP100: 6.63
Genes affected
RANBP1 (HGNC:9847): (RAN binding protein 1) This gene encodes a protein that forms a complex with Ras-related nuclear protein (Ran) and metabolizes guanoside triphosphate (GTP). This complex participates in the regulation of the cell cycle by controlling transport of proteins and nucleic acids into the nucleus. There are multiple pseudogenes for this gene on chromosomes 9, 12, 17, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
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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 |
---|---|---|---|---|---|---|---|
RANBP1 | NM_001278639.2 | c.384G>C | p.Met128Ile | missense_variant, splice_region_variant | 3/6 | ENST00000430524.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RANBP1 | ENST00000430524.6 | c.384G>C | p.Met128Ile | missense_variant, splice_region_variant | 3/6 | 3 | NM_001278639.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.000116 AC: 29AN: 250402Hom.: 0 AF XY: 0.000170 AC XY: 23AN XY: 135684
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GnomAD4 exome AF: 0.0000555 AC: 81AN: 1459818Hom.: 0 Cov.: 31 AF XY: 0.0000799 AC XY: 58AN XY: 725998
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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 | Jul 12, 2023 | The c.153G>C (p.M51I) alteration is located in exon 3 (coding exon 3) of the RANBP1 gene. This alteration results from a G to C substitution at nucleotide position 153, causing the methionine (M) at amino acid position 51 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;.;T;T;T;T;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;.;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;D;D;D;D;D;D;D
REVEL
Benign
Sift
Benign
T;.;T;T;T;T;T;T;T
Sift4G
Uncertain
D;T;T;T;T;.;.;.;.
Polyphen
0.019
.;.;.;B;.;.;.;.;.
Vest4
0.82, 0.79, 0.79
MutPred
0.41
.;.;Gain of methylation at K50 (P = 0.0206);Gain of methylation at K50 (P = 0.0206);Gain of methylation at K50 (P = 0.0206);.;.;.;.;
MVP
MPC
0.90
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at