Variant 18-8609776-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001025300.3(RAB12):c.337C>G(p.Leu113Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,146,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

RAB12
NM_001025300.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0430

Variant links:

Genes affected

RAB12 (HGNC:31332): (RAB12, member RAS oncogene family) Enables GDP binding activity. Predicted to be involved in several processes, including cellular response to insulin stimulus; endosome to lysosome transport; and secretion by cell. Predicted to act upstream of or within cellular response to interferon-gamma. Predicted to be located in lysosome; phagocytic vesicle; and recycling endosome membrane. Predicted to be active in Golgi apparatus; cytoplasmic vesicle; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RAB12 links:

RAB12 (HGNC:):

RAB12 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13158804).

BS2

High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB12	NM_001025300.3 linkuse as main transcript	c.337C>G	p.Leu113Val	missense_variant	1/6	ENST00000649141.2	NP_001020471.3	Q6IQ22
RAB12	XR_001753165.2 linkuse as main transcript	n.340C>G		non_coding_transcript_exon_variant	1/4
RAB12	XR_001753166.2 linkuse as main transcript	n.340C>G		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB12	ENST00000649141.2 linkuse as main transcript	c.337C>G	p.Leu113Val	missense_variant	1/6		NM_001025300.3	ENSP00000497886.1		A0A3B3ITT1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000174

AC:

AN:

1146160

Hom.:

Cov.:

AF XY:

0.0000127

AC XY:

AN XY:

551232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000199

Gnomad4 OTH exome

AF:

0.0000218

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

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

Sep 20, 2023

The c.49C>G (p.L17V) alteration is located in exon 1 (coding exon 1) of the RAB12 gene. This alteration results from a C to G substitution at nucleotide position 49, causing the leucine (L) at amino acid position 17 to be replaced by a valine (V). 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

0.069

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.027

.;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.46

T;T

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;N

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.0

.;N

REVEL

Benign

0.045

Sift

Benign

0.20

.;T

Sift4G

Benign

0.45

.;T

Polyphen

0.0010

.;B

Vest4

0.14

MutPred

0.27

.;Gain of sheet (P = 0.0266);

MVP

0.50

MPC

1.5

ClinPred

0.042

GERP RS

2.5

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.4

Varity_R

0.087

gMVP

0.13

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.

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