Variant 5-177301986-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001031677.4(RAB24):c.486C>G(p.Asp162Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

RAB24
NM_001031677.4 missense, splice_region

Scores

Splicing: ADA: 0.00005545

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.481

Variant links:

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 links:

RAB24 (HGNC:):

RAB24 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB24	NM_001031677.4 linkuse as main transcript	c.486C>G	p.Asp162Glu	missense_variant, splice_region_variant	7/8	ENST00000303251.11	NP_001026847.1	Q969Q5
RAB24	NM_130781.4 linkuse as main transcript	c.486C>G	p.Asp162Glu	missense_variant, splice_region_variant	8/9		NP_570137.2	Q969Q5
RAB24	NR_109789.2 linkuse as main transcript	n.1049C>G		splice_region_variant, non_coding_transcript_exon_variant	7/8
RAB24	NR_109790.2 linkuse as main transcript	n.1135C>G		splice_region_variant, non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB24	ENST00000303251.11 linkuse as main transcript	c.486C>G	p.Asp162Glu	missense_variant, splice_region_variant	7/8	1	NM_001031677.4	ENSP00000304376.6		Q969Q5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251376

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Jul 14, 2024

The c.486C>G (p.D162E) alteration is located in exon 7 (coding exon 7) of the RAB24 gene. This alteration results from a C to G substitution at nucleotide position 486, causing the aspartic acid (D) at amino acid position 162 to be replaced by a glutamic acid (E). 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

0.17

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.21

T;T;.

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.57

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.86

.;D;D

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.61

D;D;D

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.48

N;N;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.0

N;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.30

T;T;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.33

B;B;B

Vest4

0.72

MutPred

0.42

Gain of disorder (P = 0.12);Gain of disorder (P = 0.12);.;

MVP

0.80

MPC

0.88

ClinPred

0.094

GERP RS

-0.37

Varity_R

0.14

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000055

dbscSNV1_RF

Benign

0.094

SpliceAI score (max)

0.11

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over