12-69795337-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_022456.5(RAB3IP):c.881G>A(p.Cys294Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,612,072 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
RAB3IP
NM_022456.5 missense
NM_022456.5 missense
Scores
2
4
11
Clinical Significance
Conservation
PhyloP100: 6.15
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 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.27324668).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAB3IP | NM_022456.5 | c.881G>A | p.Cys294Tyr | missense_variant | 6/11 | ENST00000247833.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAB3IP | ENST00000247833.12 | c.881G>A | p.Cys294Tyr | missense_variant | 6/11 | 1 | NM_022456.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250454Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135370
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1459734Hom.: 0 Cov.: 29 AF XY: 0.0000165 AC XY: 12AN XY: 726292
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GnomAD4 genome ? AF: 0.00000656 AC: 1AN: 152338Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74496
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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 | Aug 02, 2021 | The c.929G>A (p.C310Y) alteration is located in exon 6 (coding exon 6) of the RAB3IP gene. This alteration results from a G to A substitution at nucleotide position 929, causing the cysteine (C) at amino acid position 310 to be replaced by a tyrosine (Y). 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
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T;T;T;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Uncertain
D;N;D;D;D;N;N
REVEL
Benign
Sift
Benign
T;D;T;T;T;T;T
Sift4G
Benign
T;D;T;T;T;T;T
Polyphen
0.99, 0.42, 0.93, 0.57
.;D;B;P;P;.;.
Vest4
MutPred
0.37
.;.;.;Loss of methylation at K311 (P = 0.0124);Loss of methylation at K311 (P = 0.0124);.;.;
MVP
MPC
0.43
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Score
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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