2-237575462-C-T

Variant summary

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

The NM_022449.4(RAB17):​c.454G>A​(p.Asp152Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,610,958 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000034 ( 1 hom. )

Consequence

RAB17
NM_022449.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.29
Variant links:
Genes affected
RAB17 (HGNC:16523): (RAB17, member RAS oncogene family) The Rab subfamily of small GTPases plays an important role in the regulation of membrane trafficking. RAB17 is an epithelial cell-specific GTPase (Lutcke et al., 1993 [PubMed 8486736]).[supplied by OMIM, Oct 2009]

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=0.19947451).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAB17NM_022449.4 linkc.454G>A p.Asp152Asn missense_variant Exon 5 of 6 ENST00000264601.8 NP_071894.1 Q9H0T7-1A0A024R4A4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAB17ENST00000264601.8 linkc.454G>A p.Asp152Asn missense_variant Exon 5 of 6 1 NM_022449.4 ENSP00000264601.3 Q9H0T7-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152210
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000690
AC:
17
AN:
246528
Hom.:
0
AF XY:
0.0000826
AC XY:
11
AN XY:
133250
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000329
Gnomad SAS exome
AF:
0.000236
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000358
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000343
AC:
50
AN:
1458748
Hom.:
1
Cov.:
31
AF XY:
0.0000441
AC XY:
32
AN XY:
725316
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.000246
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000189
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152210
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74354
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.454G>A (p.D152N) alteration is located in exon 5 (coding exon 4) of the RAB17 gene. This alteration results from a G to A substitution at nucleotide position 454, causing the aspartic acid (D) at amino acid position 152 to be replaced by an asparagine (N). 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
0.091
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Benign
0.12
T;.;T
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.82
T;D;T
M_CAP
Benign
0.053
D
MetaRNN
Benign
0.14
T;T;T
MetaSVM
Benign
-0.78
T
MutationAssessor
Benign
0.52
N;.;.
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-1.3
N;N;N
REVEL
Benign
0.18
Sift
Benign
0.13
T;D;T
Sift4G
Benign
0.15
T;T;.
Polyphen
0.068
B;.;.
Vest4
0.19
MutPred
0.35
Loss of ubiquitination at K155 (P = 0.069);.;.;
MVP
0.72
MPC
0.073
ClinPred
0.037
T
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.11
gMVP
0.26

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: rs767334922; hg19: chr2-238484105; API