Genetic Variant NM_016370.4:c.401C>T (chrX-103825384-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016370.4(RAB9B):c.401C>T(p.Thr134Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,163 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

RAB9B
NM_016370.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.30

Variant links:

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]

RAB9B links:

ENSG00000288597 (HGNC:):

ENSG00000288597 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
RAB9B	NM_016370.4 link	c.401C>T	p.Thr134Ile	missense_variant	Exon 3 of 3	ENST00000243298.3	NP_057454.1	Q9NP90
RAB9B	NR_146558.2 link	n.198+6676C>T		intron_variant	Intron 1 of 4
RAB9B	NR_146560.2 link	n.198+6676C>T		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB9B	ENST00000243298.3 link	c.401C>T	p.Thr134Ile	missense_variant	Exon 3 of 3	1	NM_016370.4	ENSP00000243298.2		Q9NP90

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098163

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363519

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.0094

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.94

M_CAP

Pathogenic

0.46

MetaRNN

Uncertain

0.50

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

1.7

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.37

Sift

Benign

0.034

Sift4G

Uncertain

0.021

Polyphen

0.042

Vest4

0.28

MutPred

0.53

Loss of disorder (P = 0.0202);

MVP

0.85

MPC

0.98

ClinPred

0.91

GERP RS

4.6

Varity_R

0.49

gMVP

0.46

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over