chr1-153984768-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000368575.5(RAB13):​c.138G>T​(p.Lys46Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RAB13
ENST00000368575.5 missense

Scores

8
7
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22
Variant links:
Genes affected
RAB13 (HGNC:9762): (RAB13, member RAS oncogene family) This gene is a member of the Rab family of small G proteins and plays a role in regulating membrane trafficking between trans-Golgi network (TGN) and recycling endosomes (RE). The encoded protein is involved in the assembly of tight junctions, which are components of the apical junctional complex (AJC) of epithelial cells. The AJC plays a role in forming a barrier between luminal contents and the underlying tissue. Additional functions associated with the protein include endocytic recycling of occludin, regulation of epithelial cell scattering, neuronal regeneration and regulation of neurite outgrowth. Alternately spliced transcript variants have been observed for this gene. A pseudogene associated with this gene is located on chromosome 12. [provided by RefSeq, Jan 2013]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.86

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RAB13NM_002870.5 linkuse as main transcriptc.138G>T p.Lys46Asn missense_variant 2/8 ENST00000368575.5 NP_002861.1 P51153Q504R6
RAB13NM_001272038.2 linkuse as main transcriptc.-106G>T 5_prime_UTR_variant 2/8 NP_001258967.1 P51153A0A087WWB9
RAB13XM_017001959.2 linkuse as main transcriptc.-106G>T 5_prime_UTR_variant 2/8 XP_016857448.1 A0A087WWB9
RAB13NR_073553.3 linkuse as main transcriptn.337G>T non_coding_transcript_exon_variant 2/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RAB13ENST00000368575.5 linkuse as main transcriptc.138G>T p.Lys46Asn missense_variant 2/81 NM_002870.5 ENSP00000357564.3 P51153
ENSG00000285641ENST00000648869.1 linkuse as main transcriptn.138G>T non_coding_transcript_exon_variant 2/12 ENSP00000497071.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 07, 2024The c.138G>T (p.K46N) alteration is located in exon 2 (coding exon 2) of the RAB13 gene. This alteration results from a G to T substitution at nucleotide position 138, causing the lysine (K) at amino acid position 46 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
Pathogenic
0.99
BayesDel_addAF
Uncertain
0.057
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.49
T
Eigen
Pathogenic
0.70
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.91
D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.86
D
MetaSVM
Uncertain
0.28
D
MutationAssessor
Benign
1.9
M
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.84
D
PROVEAN
Pathogenic
-4.8
D
REVEL
Pathogenic
0.68
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.72
MutPred
0.67
Loss of methylation at K46 (P = 0.0095);
MVP
0.78
MPC
1.7
ClinPred
1.0
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.91
gMVP
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-153957244; API