5-177302584-A-G

Position:

• chr5-177302584-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001031677.4(RAB24):​c.326T>C​(p.Leu109Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAB24 NM_001031677.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39199328).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB24	NM_001031677.4	c.326T>C	p.Leu109Pro	missense_variant	4/8	ENST00000303251.11	NP_001026847.1
RAB24	NM_130781.4	c.326T>C	p.Leu109Pro	missense_variant	5/9		NP_570137.2
RAB24	NR_109789.2	n.671T>C		non_coding_transcript_exon_variant	5/8
RAB24	NR_109790.2	n.757T>C		non_coding_transcript_exon_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB24	ENST00000303251.11	c.326T>C	p.Leu109Pro	missense_variant	4/8	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

Dec 10, 2024

The c.326T>C (p.L109P) alteration is located in exon 4 (coding exon 4) of the RAB24 gene. This alteration results from a T to C substitution at nucleotide position 326, causing the leucine (L) at amino acid position 109 to be replaced by a proline (P). 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	0.82
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;T;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.060
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.87	.;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	0.97	L;L;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Uncertain	0.53
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.20	T;T;T
Polyphen		0.54	P;P;P
Vest4		0.48
MutPred		0.64		Loss of stability (P = 0.0199);Loss of stability (P = 0.0199);.;
MVP		0.87
MPC		1.8
ClinPred		0.31	T
GERP RS		4.2
Varity_R		0.35
gMVP		0.83

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: chr5-176729585;