NM_030981.3:c.295G>A

Variant names:

• chr11-66275819-G-A
• rs1444836176
• NM_030981.3:c.295G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_030981.3(RAB1B):​c.295G>A​(p.Val99Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000252 in 1,586,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RAB1B NM_030981.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.60
• Publications: 1 publications found

Genes affected

RAB1B (HGNC:18370): (RAB1B, member RAS oncogene family) Members of the RAB protein family, such as RAB1B, are low molecular mass monomeric GTPases localized on the cytoplasmic surfaces of distinct membrane-bound organelles. RAB1B functions in the early secretory pathway and is essential for vesicle transport between the endoplasmic reticulum (ER) and Golgi (Chen et al., 1997 [PubMed 9030196]; Alvarez et al., 2003 [PubMed 12802079]).[supplied by OMIM, Jan 2009]

ENSG00000245156 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.756

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030981.3. 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
	RAB1B	NM_030981.3	MANE Select	c.295G>A	p.Val99Met	missense	Exon 5 of 6	NP_112243.1	Q9H0U4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB1B	ENST00000311481.11	TSL:1 MANE Select	c.295G>A	p.Val99Met	missense	Exon 5 of 6	ENSP00000310226.6	Q9H0U4
	RAB1B	ENST00000884282.1		c.439G>A	p.Val147Met	missense	Exon 6 of 7	ENSP00000554341.1
	RAB1B	ENST00000884284.1		c.295G>A	p.Val99Met	missense	Exon 5 of 6	ENSP00000554343.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1433832 Hom.: 0 Cov.: 33 AF XY: 0.00000422 AC XY: 3 AN XY: 710458

African (AFR) AF: 0.00 AC: 0 AN: 33280

American (AMR) AF: 0.00 AC: 0 AN: 38578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25522

East Asian (EAS) AF: 0.00 AC: 0 AN: 38780

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 82138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1098952

Other (OTH) AF: 0.00 AC: 0 AN: 59508

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74364

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2086

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	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	T
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Uncertain	0.38	D
PhyloP100		6.6
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.6	D
REVEL	Pathogenic	0.80
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.78		Loss of methylation at K100 (P = 0.02)
MVP		0.82
MPC		2.2
ClinPred		0.98	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.59
gMVP		0.80
Mutation Taster		=49/51	disease causing

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

Other links and lift over

dbSNP: rs1444836176; hg19: chr11-66043290;