6-57196511-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016277.5(RAB23):​c.337G>T​(p.Asp113Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D113N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RAB23
NM_016277.5 missense

Scores

1
15
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.81

Publications

0 publications found
Variant links:
Genes affected
RAB23 (HGNC:14263): (RAB23, member RAS oncogene family) This gene encodes a small GTPase of the Ras superfamily. Rab proteins are involved in the regulation of diverse cellular functions associated with intracellular membrane trafficking, including autophagy and immune response to bacterial infection. The encoded protein may play a role in central nervous system development by antagonizing sonic hedgehog signaling. Disruption of this gene has been implicated in Carpenter syndrome as well as cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
RAB23 Gene-Disease associations (from GenCC):
  • RAB23-related Carpenter syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, G2P
  • Carpenter syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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
RAB23NM_016277.5 linkc.337G>T p.Asp113Tyr missense_variant Exon 4 of 7 ENST00000468148.6 NP_057361.3 Q9ULC3A0A024RD41

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAB23ENST00000468148.6 linkc.337G>T p.Asp113Tyr missense_variant Exon 4 of 7 1 NM_016277.5 ENSP00000417610.1 Q9ULC3
RAB23ENST00000317483.4 linkc.337G>T p.Asp113Tyr missense_variant Exon 4 of 7 1 ENSP00000320413.3 Q9ULC3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251282
AF XY:
0.00
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 FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461746
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727168
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33478
American (AMR)
AF:
0.00
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26128
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39666
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
0.0000374
AC:
2
AN:
53412
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111936
Other (OTH)
AF:
0.00
AC:
0
AN:
60386
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.029673), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.55
D;D
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;.
M_CAP
Benign
0.069
D
MetaRNN
Uncertain
0.62
D;D
MetaSVM
Uncertain
-0.19
T
MutationAssessor
Uncertain
2.2
M;M
PhyloP100
5.8
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-3.1
D;D
REVEL
Uncertain
0.52
Sift
Uncertain
0.0060
D;D
Sift4G
Uncertain
0.0080
D;D
Polyphen
0.33
B;B
Vest4
0.67
MutPred
0.55
Gain of phosphorylation at D113 (P = 0.1168);Gain of phosphorylation at D113 (P = 0.1168);
MVP
0.86
MPC
0.34
ClinPred
0.86
D
GERP RS
6.0
Varity_R
0.56
gMVP
0.68
Mutation Taster
=29/71
disease causing

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

Other links and lift over

dbSNP: rs748398827; hg19: chr6-57061309; API