rs398123044
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001017979.3(RAB28):c.409C>T(p.Arg137Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000558 in 1,612,062 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 Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
RAB28
NM_001017979.3 stop_gained
NM_001017979.3 stop_gained
Scores
2
2
3
Clinical Significance
Conservation
PhyloP100: 4.26
Genes affected
RAB28 (HGNC:9768): (RAB28, member RAS oncogene family) This gene encodes a member of the Rab subfamily of Ras-related small GTPases. The encoded protein may be involved in regulating intracellular trafficking. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 9 and X. [provided by RefSeq, Apr 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 4-13381577-G-A is Pathogenic according to our data. Variant chr4-13381577-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 60755.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-13381577-G-A is described in Lovd as [Pathogenic]. Variant chr4-13381577-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAB28 | NM_001017979.3 | c.409C>T | p.Arg137Ter | stop_gained | 5/7 | ENST00000330852.10 | |
RAB28 | NM_004249.4 | c.409C>T | p.Arg137Ter | stop_gained | 5/8 | ENST00000288723.9 | |
RAB28 | NM_001159601.2 | c.409C>T | p.Arg137Ter | stop_gained | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAB28 | ENST00000330852.10 | c.409C>T | p.Arg137Ter | stop_gained | 5/7 | 1 | NM_001017979.3 | P4 | |
RAB28 | ENST00000288723.9 | c.409C>T | p.Arg137Ter | stop_gained | 5/8 | 1 | NM_004249.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151996Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250476Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135462
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1460066Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 726336
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151996Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74218
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Cone-rod dystrophy 18 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 11, 2013 | - - |
Cone-rod dystrophy Pathogenic:1
Pathogenic, no assertion criteria provided | research | Sharon lab, Hadassah-Hebrew University Medical Center | Jun 23, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Benign
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;A
Vest4
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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