rs781609607

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022337.3(RAB38):​c.457G>T​(p.Val153Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V153I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

RAB38
NM_022337.3 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.62
Variant links:
Genes affected
RAB38 (HGNC:9776): (RAB38, member RAS oncogene family) Enables several functions, including AP-1 adaptor complex binding activity; AP-3 adaptor complex binding activity; and BLOC-2 complex binding activity. Involved in several processes, including endosome to melanosome transport; melanosome assembly; and phagosome acidification. Located in several cellular components, including cytoplasmic vesicle; lysosome; and mitochondria-associated endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25033307).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAB38NM_022337.3 linkc.457G>T p.Val153Leu missense_variant Exon 2 of 3 ENST00000243662.11 NP_071732.1 P57729A0A024R191
RAB38XM_017017455.3 linkc.457G>T p.Val153Leu missense_variant Exon 2 of 4 XP_016872944.1
RAB38XM_017017456.3 linkc.457G>T p.Val153Leu missense_variant Exon 2 of 4 XP_016872945.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAB38ENST00000243662.11 linkc.457G>T p.Val153Leu missense_variant Exon 2 of 3 1 NM_022337.3 ENSP00000243662.5 P57729
RAB38ENST00000526372.1 linkc.451G>T p.Val151Leu missense_variant Exon 2 of 3 3 ENSP00000433317.1 H0YDB7
RAB38ENST00000531138.1 linkc.250+25482G>T intron_variant Intron 1 of 1 2 ENSP00000435340.1 H0YEA4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.0017
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.28
T
Eigen
Benign
-0.13
Eigen_PC
Benign
0.10
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.85
D
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.25
T
MetaSVM
Benign
-0.84
T
MutationAssessor
Benign
0.050
N
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.23
Sift
Benign
0.49
T
Sift4G
Benign
0.67
T
Polyphen
0.022
B
Vest4
0.52
MutPred
0.47
Gain of ubiquitination at K148 (P = 0.0931);
MVP
0.75
MPC
0.092
ClinPred
0.69
D
GERP RS
5.5
Varity_R
0.54
gMVP
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs781609607; hg19: chr11-87882869; API