Variant X-13709340-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000464506.2(RAB9A):c.594A>T(p.Ser198Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00586 in 1,197,161 control chromosomes in the GnomAD database, including 14 homozygotes. There are 2,357 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 0 hom., 170 hem., cov: 23)

Exomes 𝑓: 0.0059 ( 14 hom. 2187 hem. )

Consequence

RAB9A
ENST00000464506.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.842

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 Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant X-13709340-A-T is Benign according to our data. Variant chrX-13709340-A-T is described in ClinVar as [Benign]. Clinvar id is 782175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.842 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 170 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB9A	NM_004251.5 linkuse as main transcript	c.594A>T	p.Ser198Ser	synonymous_variant	3/3	ENST00000464506.2	NP_004242.1	P51151A0A024RBV5
RAB9A	NM_001195328.2 linkuse as main transcript	c.594A>T	p.Ser198Ser	synonymous_variant	2/2		NP_001182257.1	P51151A0A024RBV5
RAB9A	XM_047442644.1 linkuse as main transcript	c.594A>T	p.Ser198Ser	synonymous_variant	3/3		XP_047298600.1
RAB9A	XM_047442645.1 linkuse as main transcript	c.594A>T	p.Ser198Ser	synonymous_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.594A>T	p.Ser198Ser	synonymous_variant	3/3	1	NM_004251.5	ENSP00000420127.1		P51151
RAB9A	ENST00000618931.2 linkuse as main transcript	c.594A>T	p.Ser198Ser	synonymous_variant	2/2	2		ENSP00000480777.1		P51151

Frequencies

GnomAD3 genomes

AF:

0.00541

AC:

607

AN:

112195

Hom.:

Cov.:

AF XY:

0.00495

AC XY:

170

AN XY:

34365

show subpopulations

Gnomad AFR

AF:

0.00832

Gnomad AMI

AF:

0.00145

Gnomad AMR

AF:

0.00208

Gnomad ASJ

AF:

0.00113

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00821

Gnomad FIN

AF:

0.00278

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00511

Gnomad OTH

AF:

0.00866

GnomAD3 exomes

AF:

0.00492

AC:

843

AN:

171403

Hom.:

AF XY:

0.00514

AC XY:

297

AN XY:

57757

show subpopulations

Gnomad AFR exome

AF:

0.00939

Gnomad AMR exome

AF:

0.00222

Gnomad ASJ exome

AF:

0.00214

Gnomad EAS exome

AF:

0.000148

Gnomad SAS exome

AF:

0.00693

Gnomad FIN exome

AF:

0.00335

Gnomad NFE exome

AF:

0.00608

Gnomad OTH exome

AF:

0.00380

GnomAD4 exome

AF:

0.00591

AC:

6410

AN:

1084911

Hom.:

Cov.:

AF XY:

0.00619

AC XY:

2187

AN XY:

353075

show subpopulations

Gnomad4 AFR exome

AF:

0.0110

Gnomad4 AMR exome

AF:

0.00244

Gnomad4 ASJ exome

AF:

0.00181

Gnomad4 EAS exome

AF:

0.0000667

Gnomad4 SAS exome

AF:

0.00806

Gnomad4 FIN exome

AF:

0.00353

Gnomad4 NFE exome

AF:

0.00617

Gnomad4 OTH exome

AF:

0.00534

GnomAD4 genome

AF:

0.00543

AC:

609

AN:

112250

Hom.:

Cov.:

AF XY:

0.00494

AC XY:

170

AN XY:

34428

show subpopulations

Gnomad4 AFR

AF:

0.00840

Gnomad4 AMR

AF:

0.00208

Gnomad4 ASJ

AF:

0.00113

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00786

Gnomad4 FIN

AF:

0.00278

Gnomad4 NFE

AF:

0.00511

Gnomad4 OTH

AF:

0.00855

Alfa

AF:

0.00509

Hom.:

Bravo

AF:

0.00566

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.6

DANN

Benign

0.83

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