Genetic Variant RAB12:p.Arg106Trp (chr18-8609755-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001025300.3(RAB12):c.316C>T(p.Arg106Trp) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R106G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RAB12
NM_001025300.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.802

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1917085).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025300.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB12	NM_001025300.3	MANE Select	c.316C>T	p.Arg106Trp	missense	Exon 1 of 6	NP_001020471.3	A0A3B3ITT1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB12	ENST00000649141.2	MANE Select	c.316C>T	p.Arg106Trp	missense	Exon 1 of 6	ENSP00000497886.1	A0A3B3ITT1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1092878

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

521756

African (AFR)

AF:

0.00

AC:

AN:

21706

American (AMR)

AF:

0.00

AC:

AN:

7290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13016

East Asian (EAS)

AF:

0.00

AC:

AN:

23622

South Asian (SAS)

AF:

0.00

AC:

AN:

24628

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31680

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2898

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

925304

Other (OTH)

AF:

0.00

AC:

AN:

42734

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.73

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

0.80

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.26

REVEL

Benign

0.072

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.025

Polyphen

0.0010

Vest4

0.31

MutPred

0.36

Loss of methylation at R10 (P = 0.0177)

MVP

0.31

MPC

1.5

ClinPred

0.82

GERP RS

2.5

PromoterAI

-0.14

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

4.3

Varity_R

0.14

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over