NM_001025300.3:c.316C>G

Variant names:

• chr18-8609755-C-G
• rs2096002619
• NM_001025300.3:c.316C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001025300.3(RAB12):​c.316C>G​(p.Arg106Gly) 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. 14/22 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)
• Consequence: RAB12 NM_001025300.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.802
• Publications: 0 publications found

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]

ACMG classification

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=0.15324488).

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>G	p.Arg106Gly	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>G	p.Arg106Gly	missense	Exon 1 of 6	ENSP00000497886.1	A0A3B3ITT1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	23
DANN	Benign	0.93
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.80
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.097
Sift	Benign	0.27	T
Sift4G	Benign	0.32	T
Polyphen		0.0	B
Vest4		0.32
MutPred		0.36		Loss of helix (P = 0.0123)
MVP		0.37
MPC		1.8
ClinPred		0.73	D
GERP RS		2.5
PromoterAI		-0.10	Neutral
Varity_R		0.086
gMVP		0.55

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

Other links and lift over

dbSNP: rs2096002619; hg19: chr18-8609753;