chrX-103825699-G-C

Variant names:

• chrX-103825699-G-C
• NM_016370.4:c.86C>G

Variant summary

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

The NM_016370.4(RAB9B):​c.86C>G​(p.Thr29Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: RAB9B NM_016370.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 10.0
• Publications: 0 publications found

Genes affected

RAB9B (HGNC:14090): (RAB9B, member RAS oncogene family) This gene encodes a member of a subfamily of RAS small guanosine triphosphate (GTP)-binding proteins that regulate membrane trafficking. The encoded protein may be involved in endosome-to-Golgi transport. [provided by RefSeq, Jan 2010]

ENSG00000288597 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016370.4. 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
	RAB9B	NM_016370.4	MANE Select	c.86C>G	p.Thr29Ser	missense	Exon 3 of 3	NP_057454.1	Q9NP90
	RAB9B	NR_146558.2		n.198+6361C>G		intron	N/A
	RAB9B	NR_146560.2		n.198+6361C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB9B	ENST00000243298.3	TSL:1 MANE Select	c.86C>G	p.Thr29Ser	missense	Exon 3 of 3	ENSP00000243298.2	Q9NP90
	RAB9B	ENST00000873736.1		c.86C>G	p.Thr29Ser	missense	Exon 2 of 2	ENSP00000543795.1
	RAB9B	ENST00000963274.1		c.86C>G	p.Thr29Ser	missense	Exon 2 of 2	ENSP00000633333.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions as Germline

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	0.16
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.86	D
M_CAP	Pathogenic	0.46	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.51	N
PhyloP100		10
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	0.82	N
REVEL	Uncertain	0.30
Sift	Benign	0.27	T
Sift4G	Benign	0.25	T
Polyphen		0.0	B
Vest4		0.57
MutPred		0.41		Gain of disorder (P = 0.0453)
MVP		0.81
MPC		1.0
ClinPred		0.65	D
GERP RS		6.0
Varity_R		0.34
gMVP		0.63
Mutation Taster		=27/73	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chrX-103080629;