Genetic Variant RAB12:p.Gln104Arg (chr18-8609750-A-G) – 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.311A>G(p.Gln104Arg) 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. 16/22 in silico tools predict 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. Q104P) 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: 2.04

Publications

1 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=0.12497565).

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.311A>G	p.Gln104Arg	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.311A>G	p.Gln104Arg	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:

1081206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

515408

African (AFR)

AF:

0.00

AC:

AN:

21476

American (AMR)

AF:

0.00

AC:

AN:

7096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12692

East Asian (EAS)

AF:

0.00

AC:

AN:

23084

South Asian (SAS)

AF:

0.00

AC:

AN:

23308

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2842

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

918288

Other (OTH)

AF:

0.00

AC:

AN:

42036

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.017

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.38

M_CAP

Benign

0.041

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

2.0

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.16

REVEL

Benign

0.085

Sift

Benign

0.18

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.17

MutPred

0.12

Gain of MoRF binding (P = 0.0153)

MVP

0.37

MPC

1.6

ClinPred

0.16

GERP RS

2.4

PromoterAI

0.15

Neutral

(source)

Varity_R

0.054

gMVP

0.20

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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