chr19-5932512-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_007322.3(RANBP3):c.505C>T(p.Arg169Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000123 in 1,613,710 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 (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
RANBP3
NM_007322.3 missense
NM_007322.3 missense
Scores
4
4
10
Clinical Significance
Conservation
PhyloP100: 5.51
Genes affected
RANBP3 (HGNC:9850): (RAN binding protein 3) This gene encodes a protein with a RanBD1 domain that is found in both the nucleus and cytoplasm. This protein plays a role in nuclear export as part of a heteromeric complex. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.34195548).
BS2
?
High AC in GnomAd at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RANBP3 | NM_007322.3 | c.505C>T | p.Arg169Trp | missense_variant | 7/17 | ENST00000340578.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RANBP3 | ENST00000340578.10 | c.505C>T | p.Arg169Trp | missense_variant | 7/17 | 1 | NM_007322.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000985 AC: 15AN: 152232Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000442 AC: 11AN: 249062Hom.: 0 AF XY: 0.0000666 AC XY: 9AN XY: 135212
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GnomAD4 exome AF: 0.000126 AC: 184AN: 1461478Hom.: 0 Cov.: 30 AF XY: 0.000117 AC XY: 85AN XY: 727042
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GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74372
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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 | Dec 14, 2022 | The c.505C>T (p.R169W) alteration is located in exon 7 (coding exon 7) of the RANBP3 gene. This alteration results from a C to T substitution at nucleotide position 505, causing the arginine (R) at amino acid position 169 to be replaced by a tryptophan (W). 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
Pathogenic
Dann
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;.;D;.
REVEL
Benign
Sift
Benign
T;D;.;D;.
Sift4G
Benign
T;T;T;T;.
Polyphen
D;D;D;D;.
Vest4
MVP
MPC
1.4
ClinPred
D
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