6-146543944-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006834.5(RAB32):​c.73C>T​(p.Leu25Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,612,112 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

RAB32
NM_006834.5 missense

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02
Variant links:
Genes affected
RAB32 (HGNC:9772): (RAB32, member RAS oncogene family) The protein encoded by this gene anchors the type II regulatory subunit of protein kinase A to the mitochondrion and aids in mitochondrial fission. The encoded protein also appears to be involved in autophagy and melanosome secretion. Variations in this gene may be linked to leprosy. [provided by RefSeq, Dec 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAB32NM_006834.5 linkc.73C>T p.Leu25Phe missense_variant Exon 1 of 3 ENST00000367495.4 NP_006825.1 Q13637

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAB32ENST00000367495.4 linkc.73C>T p.Leu25Phe missense_variant Exon 1 of 3 1 NM_006834.5 ENSP00000356465.3 Q13637

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
151930
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000283
AC:
7
AN:
247492
Hom.:
0
AF XY:
0.0000223
AC XY:
3
AN XY:
134626
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:
0.0000541
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.00000822
AC:
12
AN:
1460066
Hom.:
0
Cov.:
31
AF XY:
0.00000826
AC XY:
6
AN XY:
726344
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152046
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000450
Hom.:
0
Bravo
AF:
0.0000113
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 05, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.73C>T (p.L25F) alteration is located in exon 1 (coding exon 1) of the RAB32 gene. This alteration results from a C to T substitution at nucleotide position 73, causing the leucine (L) at amino acid position 25 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
Pathogenic
0.74
BayesDel_addAF
Uncertain
0.054
T
BayesDel_noAF
Uncertain
-0.030
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.24
T
Eigen
Benign
-0.016
Eigen_PC
Benign
-0.015
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.90
D
M_CAP
Pathogenic
0.54
D
MetaRNN
Uncertain
0.68
D
MetaSVM
Benign
-0.38
T
MutationAssessor
Benign
1.8
L
PrimateAI
Pathogenic
0.89
D
PROVEAN
Uncertain
-3.9
D
REVEL
Uncertain
0.61
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0030
D
Polyphen
0.56
P
Vest4
0.72
MVP
0.78
MPC
0.16
ClinPred
0.33
T
GERP RS
3.8
Varity_R
0.91
gMVP
0.59

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: rs374801392; hg19: chr6-146865080; API