chr12-69784766-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_022456.5(RAB3IP):c.557G>A(p.Arg186Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000892 in 1,457,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
RAB3IP
NM_022456.5 missense
NM_022456.5 missense
Scores
7
6
4
Clinical Significance
Conservation
PhyloP100: 9.18
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 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.809
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAB3IP | NM_022456.5 | c.557G>A | p.Arg186Gln | missense_variant | 4/11 | ENST00000247833.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAB3IP | ENST00000247833.12 | c.557G>A | p.Arg186Gln | missense_variant | 4/11 | 1 | NM_022456.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249196Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134764
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GnomAD4 exome AF: 0.00000892 AC: 13AN: 1457326Hom.: 0 Cov.: 28 AF XY: 0.00000827 AC XY: 6AN XY: 725120
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GnomAD4 genome ? Cov.: 32
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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 | Feb 23, 2023 | The c.605G>A (p.R202Q) alteration is located in exon 4 (coding exon 4) of the RAB3IP gene. This alteration results from a G to A substitution at nucleotide position 605, causing the arginine (R) at amino acid position 202 to be replaced by a glutamine (Q). 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
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D;D;D
REVEL
Uncertain
Sift
Benign
T;T;T;T;T;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
1.0, 0.99, 1.0
.;D;D;D;D;.
Vest4
MutPred
0.63
.;.;.;Gain of ubiquitination at K200 (P = 0.115);Gain of ubiquitination at K200 (P = 0.115);.;
MVP
MPC
0.55
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