Variant X-13709087-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004251.5(RAB9A):c.341C>T(p.Pro114Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000172 in 1,209,663 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 74 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 7 hem., cov: 23)

Exomes 𝑓: 0.00018 ( 0 hom. 67 hem. )

Consequence

RAB9A
NM_004251.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.93

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RAB9A	NM_004251.5 linkuse as main transcript	c.341C>T	p.Pro114Leu	missense_variant	3/3	ENST00000464506.2	NP_004242.1
RAB9A	NM_001195328.2 linkuse as main transcript	c.341C>T	p.Pro114Leu	missense_variant	2/2		NP_001182257.1
RAB9A	XM_047442644.1 linkuse as main transcript	c.341C>T	p.Pro114Leu	missense_variant	3/3		XP_047298600.1
RAB9A	XM_047442645.1 linkuse as main transcript	c.341C>T	p.Pro114Leu	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.341C>T	p.Pro114Leu	missense_variant	3/3	1	NM_004251.5	ENSP00000420127	P1
RAB9A	ENST00000618931.2 linkuse as main transcript	c.341C>T	p.Pro114Leu	missense_variant	2/2	2		ENSP00000480777	P1

Frequencies

GnomAD3 genomes

AF:

0.000135

AC:

AN:

111452

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

AN XY:

33644

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00146

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:

0.000264

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000142

AC:

AN:

183256

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

67758

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000318

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000176

AC:

193

AN:

1098156

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

AN XY:

363514

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:

0.000224

Gnomad4 OTH exome

AF:

0.0000868

GnomAD4 genome

AF:

0.000135

AC:

AN:

111507

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

AN XY:

33709

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000264

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.000132

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ExAC

AF:

0.000165

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

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

Jun 05, 2023

The c.341C>T (p.P114L) alteration is located in exon 3 (coding exon 1) of the RAB9A gene. This alteration results from a C to T substitution at nucleotide position 341, causing the proline (P) at amino acid position 114 to be replaced by a leucine (L). 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

0.23

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

D;D

FATHMM_MKL

Uncertain

0.90

LIST_S2

Pathogenic

0.99

.;D

M_CAP

Pathogenic

0.58

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.3

L;L

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.79

PROVEAN

Pathogenic

-6.7

D;.

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.81

P;P

Vest4

0.57

MVP

0.79

MPC

1.8

ClinPred

0.48

GERP RS

4.6

Varity_R

0.84

gMVP

0.81

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over