5-177302445-G-C

Position:

• chr5-177302445-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001031677.4(RAB24):​c.385C>G​(p.Arg129Gly) 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 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: not found (cov: 32)
• Consequence: RAB24 NM_001031677.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.505

Genes affected

RAB24 (HGNC:9765): (RAB24, member RAS oncogene family) RAB24 is a small GTPase of the Rab subfamily of Ras-related proteins that regulate intracellular protein trafficking (Olkkonen et al., 1993 [PubMed 8126105]).[supplied by OMIM, Aug 2009]

RAB24 (HGNC:):

ACMG classification

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=0.25629833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB24	NM_001031677.4	c.385C>G	p.Arg129Gly	missense_variant	5/8	ENST00000303251.11	NP_001026847.1
RAB24	NM_130781.4	c.385C>G	p.Arg129Gly	missense_variant	6/9		NP_570137.2
RAB24	NR_109789.2	n.730C>G		non_coding_transcript_exon_variant	6/8
RAB24	NR_109790.2	n.816C>G		non_coding_transcript_exon_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB24	ENST00000303251.11	c.385C>G	p.Arg129Gly	missense_variant	5/8	1	NM_001031677.4	ENSP00000304376.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.385C>G (p.R129G) alteration is located in exon 5 (coding exon 5) of the RAB24 gene. This alteration results from a C to G substitution at nucleotide position 385, causing the arginine (R) at amino acid position 129 to be replaced by a glycine (G). 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	0.28
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.25	T;T;.
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.85	.;T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.64	N;N;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.52	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.41	T;T;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.0020	B;B;B
Vest4		0.59
MutPred		0.41		Loss of solvent accessibility (P = 0.0509);Loss of solvent accessibility (P = 0.0509);.;
MVP		0.40
MPC		1.1
ClinPred		0.22	T
GERP RS		2.0
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Varity_R		0.17
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr5-176729446;