11-82982186-C-A

Variant summary

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

The NM_001286060.2(RAB30):​c.591G>T​(p.Leu197Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 6.8e-7 ( 0 hom. )

Consequence

RAB30
NM_001286060.2 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.92
Variant links:
Genes affected
RAB30 (HGNC:9770): (RAB30, member RAS oncogene family) Predicted to enable GTP binding activity and GTPase activity. Involved in Golgi organization. Located in Golgi cisterna; cis-Golgi network; and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.18401596).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAB30NM_001286060.2 linkc.591G>T p.Leu197Phe missense_variant Exon 5 of 5 ENST00000527633.6 NP_001272989.1 Q15771-1A8K5R1
RAB30NM_001286059.2 linkc.591G>T p.Leu197Phe missense_variant Exon 5 of 5 NP_001272988.1 Q15771-1A8K5R1
RAB30NM_001286061.1 linkc.591G>T p.Leu197Phe missense_variant Exon 5 of 5 NP_001272990.1 Q15771-1A8K5R1
RAB30NM_014488.5 linkc.591G>T p.Leu197Phe missense_variant Exon 6 of 6 NP_055303.2 Q15771-1A8K5R1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAB30ENST00000527633.6 linkc.591G>T p.Leu197Phe missense_variant Exon 5 of 5 1 NM_001286060.2 ENSP00000435089.1 Q15771-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152202
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251074
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135664
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461852
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152202
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 23, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.591G>T (p.L197F) alteration is located in exon 6 (coding exon 4) of the RAB30 gene. This alteration results from a G to T substitution at nucleotide position 591, causing the leucine (L) at amino acid position 197 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.078
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.033
T;T;T;.;T
Eigen
Benign
-0.15
Eigen_PC
Benign
0.082
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.86
D;.;.;D;.
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.18
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;N;N;.;N
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-0.40
.;N;N;N;N
REVEL
Benign
0.044
Sift
Benign
0.13
.;T;T;T;T
Sift4G
Benign
0.63
T;T;T;T;T
Polyphen
0.080
B;B;B;.;B
Vest4
0.34
MutPred
0.33
Gain of methylation at K192 (P = 0.0775);Gain of methylation at K192 (P = 0.0775);Gain of methylation at K192 (P = 0.0775);.;Gain of methylation at K192 (P = 0.0775);
MVP
0.29
MPC
0.90
ClinPred
0.37
T
GERP RS
5.0
Varity_R
0.15
gMVP
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs749170427; hg19: chr11-82693228; API