X-103825699-G-C

Position:

• chrX-103825699-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB9B	NM_016370.4	c.86C>G	p.Thr29Ser	missense_variant	3/3	ENST00000243298.3	NP_057454.1
RAB9B	NR_146558.2	n.198+6361C>G		intron_variant
RAB9B	NR_146560.2	n.198+6361C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB9B	ENST00000243298.3	c.86C>G	p.Thr29Ser	missense_variant	3/3	1	NM_016370.4	ENSP00000243298.2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 04, 2024

The c.86C>G (p.T29S) alteration is located in exon 3 (coding exon 1) of the RAB9B gene. This alteration results from a C to G substitution at nucleotide position 86, causing the threonine (T) at amino acid position 29 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-103080629;