chr12-69794455-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_022456.5(RAB3IP):c.625A>G(p.Arg209Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000825 in 1,612,486 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 0.000090 ( 2 hom. )
Consequence
RAB3IP
NM_022456.5 missense
NM_022456.5 missense
Scores
3
7
7
Clinical Significance
Conservation
PhyloP100: 2.09
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 Likely_benign. Variant got -2 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.12807113).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAB3IP | NM_022456.5 | c.625A>G | p.Arg209Gly | missense_variant | 5/11 | ENST00000247833.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAB3IP | ENST00000247833.12 | c.625A>G | p.Arg209Gly | missense_variant | 5/11 | 1 | NM_022456.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000128 AC: 32AN: 249206Hom.: 1 AF XY: 0.000208 AC XY: 28AN XY: 134646
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GnomAD4 exome AF: 0.0000904 AC: 132AN: 1460262Hom.: 2 Cov.: 30 AF XY: 0.000136 AC XY: 99AN XY: 726308
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74370
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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 | Jun 01, 2023 | The c.673A>G (p.R225G) alteration is located in exon 5 (coding exon 5) of the RAB3IP gene. This alteration results from a A to G substitution at nucleotide position 673, causing the arginine (R) at amino acid position 225 to be replaced by a glycine (G). 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
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D;.;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D
Polyphen
0.76, 0.95, 0.72, 0.97
.;P;P;P;D;.;.
Vest4
MutPred
0.63
.;.;.;Loss of MoRF binding (P = 0.0329);Loss of MoRF binding (P = 0.0329);.;.;
MVP
MPC
0.36
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