Variant X-13709341-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004251.5(RAB9A):c.595T>C(p.Ser199Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000921 in 1,085,904 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.2e-7 ( 0 hom. 0 hem. )

Consequence

RAB9A
NM_004251.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.88

Variant links:

Genes affected

RAB9A (HGNC:9792): (RAB9A, member RAS oncogene family) Enables GDP binding activity; GTP binding activity; and GTPase activity. Involved in negative regulation by host of symbiont catalytic activity; positive regulation of exocytosis; and regulation of protein localization. Located in late endosome; lysosome; and phagocytic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

RAB9A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33434206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RAB9A	NM_004251.5 linkuse as main transcript	c.595T>C	p.Ser199Pro	missense_variant	3/3	ENST00000464506.2	NP_004242.1
RAB9A	NM_001195328.2 linkuse as main transcript	c.595T>C	p.Ser199Pro	missense_variant	2/2		NP_001182257.1
RAB9A	XM_047442644.1 linkuse as main transcript	c.595T>C	p.Ser199Pro	missense_variant	3/3		XP_047298600.1
RAB9A	XM_047442645.1 linkuse as main transcript	c.595T>C	p.Ser199Pro	missense_variant	3/3		XP_047298601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB9A	ENST00000464506.2 linkuse as main transcript	c.595T>C	p.Ser199Pro	missense_variant	3/3	1	NM_004251.5	ENSP00000420127	P1
RAB9A	ENST00000618931.2 linkuse as main transcript	c.595T>C	p.Ser199Pro	missense_variant	2/2	2		ENSP00000480777	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.21e-7

AC:

AN:

1085904

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

353652

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:

0.00000120

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2023

The c.595T>C (p.S199P) alteration is located in exon 3 (coding exon 1) of the RAB9A gene. This alteration results from a T to C substitution at nucleotide position 595, causing the serine (S) at amino acid position 199 to be replaced by a proline (P). 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

0.10

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

T;T

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.68

.;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.33

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

0.98

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.0

D;.

REVEL

Benign

0.13

Sift

Benign

0.068

T;.

Sift4G

Benign

0.17

T;T

Polyphen

0.71

P;P

Vest4

0.17

MutPred

0.30

Gain of catalytic residue at S199 (P = 6e-04);Gain of catalytic residue at S199 (P = 6e-04);

MVP

0.83

MPC

1.3

ClinPred

0.91

GERP RS

5.4

Varity_R

0.63

gMVP

0.59

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over