12-69801681-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_022456.5(RAB3IP):c.1090C>T(p.Arg364Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000868 in 1,612,430 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 28)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
RAB3IP
NM_022456.5 missense
NM_022456.5 missense
Scores
2
6
9
Clinical Significance
Conservation
PhyloP100: 5.76
Genes affected
RAB3IP (HGNC:16508): (RAB3A interacting protein) Enables guanyl-nucleotide exchange factor activity and identical protein binding activity. Involved in cilium assembly; protein localization to organelle; and protein targeting to membrane. Located in centrosome; cytosol; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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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 |
---|---|---|---|---|---|---|---|
RAB3IP | NM_022456.5 | c.1090C>T | p.Arg364Trp | missense_variant | 8/11 | ENST00000247833.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAB3IP | ENST00000247833.12 | c.1090C>T | p.Arg364Trp | missense_variant | 8/11 | 1 | NM_022456.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151756Hom.: 0 Cov.: 28
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251090Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135696
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GnomAD4 exome AF: 0.00000822 AC: 12AN: 1460674Hom.: 0 Cov.: 30 AF XY: 0.00000826 AC XY: 6AN XY: 726638
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151756Hom.: 0 Cov.: 28 AF XY: 0.0000135 AC XY: 1AN XY: 74088
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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 | Apr 28, 2022 | The c.1138C>T (p.R380W) alteration is located in exon 8 (coding exon 8) of the RAB3IP gene. This alteration results from a C to T substitution at nucleotide position 1138, causing the arginine (R) at amino acid position 380 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
Uncertain
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;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;D;T;D;D;D;D
Sift4G
Benign
T;D;T;D;D;D;D
Polyphen
0.99, 0.99, 1.0
.;D;D;D;.;.;.
Vest4
MutPred
0.46
.;.;Gain of ubiquitination at K383 (P = 0.0548);Gain of ubiquitination at K383 (P = 0.0548);.;.;.;
MVP
MPC
0.42
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