3-120709797-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_173825.5(RABL3):c.251T>C(p.Phe84Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000645 in 1,611,284 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: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000065 ( 0 hom. )
Consequence
RABL3
NM_173825.5 missense
NM_173825.5 missense
Scores
12
5
2
Clinical Significance
Conservation
PhyloP100: 8.32
Genes affected
RABL3 (HGNC:18072): (RAB, member of RAS oncogene family like 3) Predicted to enable GTP binding activity; GTPase activity; and protein homodimerization activity. Involved in regulation of Ras protein signal transduction and regulation of protein lipidation. Predicted to be active in endomembrane system. Implicated in pancreatic cancer. [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.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.932
BS2
?
High AC in GnomAd at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RABL3 | NM_173825.5 | c.251T>C | p.Phe84Ser | missense_variant | 3/8 | ENST00000273375.8 | |
RABL3 | NM_001363965.1 | c.251T>C | p.Phe84Ser | missense_variant | 3/9 | ||
RABL3 | NM_001363964.1 | c.251T>C | p.Phe84Ser | missense_variant | 3/7 | ||
RABL3 | NR_157022.1 | n.565T>C | non_coding_transcript_exon_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RABL3 | ENST00000273375.8 | c.251T>C | p.Phe84Ser | missense_variant | 3/8 | 1 | NM_173825.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152088Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000440 AC: 11AN: 250142Hom.: 0 AF XY: 0.0000518 AC XY: 7AN XY: 135240
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GnomAD4 exome AF: 0.0000651 AC: 95AN: 1459196Hom.: 0 Cov.: 29 AF XY: 0.0000716 AC XY: 52AN XY: 725974
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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 09, 2021 | The c.251T>C (p.F84S) alteration is located in exon 3 (coding exon 3) of the RABL3 gene. This alteration results from a T to C substitution at nucleotide position 251, causing the phenylalanine (F) at amino acid position 84 to be replaced by a serine (S). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Gain of disorder (P = 0.0042);Gain of disorder (P = 0.0042);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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