Variant X-154438512-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000447750.7(GDI1):c.46-11C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000424 in 1,119,127 control chromosomes in the GnomAD database, including 1 homozygotes. There are 132 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., 52 hem., cov: 23)

Exomes 𝑓: 0.00027 ( 1 hom. 80 hem. )

Consequence

GDI1
ENST00000447750.7 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0002234

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.551

Variant links:

Genes affected

GDI1 (HGNC:4226): (GDP dissociation inhibitor 1) GDP dissociation inhibitors are proteins that regulate the GDP-GTP exchange reaction of members of the rab family, small GTP-binding proteins of the ras superfamily, that are involved in vesicular trafficking of molecules between cellular organelles. GDIs slow the rate of dissociation of GDP from rab proteins and release GDP from membrane-bound rabs. GDI1 is expressed primarily in neural and sensory tissues. Mutations in GDI1 have been linked to X-linked nonspecific cognitive disability. [provided by RefSeq, Jul 2008]

GDI1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant X-154438512-C-A is Benign according to our data. Variant chrX-154438512-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 376795.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 52 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDI1	NM_001493.3 linkuse as main transcript	c.46-11C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000447750.7	NP_001484.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDI1	ENST00000447750.7 linkuse as main transcript	c.46-11C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001493.3	ENSP00000394071	P1

Frequencies

GnomAD3 genomes

AF:

0.00178

AC:

199

AN:

111949

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

AN XY:

34121

show subpopulations

Gnomad AFR

AF:

0.00621

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000376

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:

0.0000189

Gnomad OTH

AF:

0.00200

GnomAD3 exomes

AF:

0.000575

AC:

105

AN:

182738

Hom.:

AF XY:

0.000267

AC XY:

AN XY:

67418

show subpopulations

Gnomad AFR exome

AF:

0.00696

Gnomad AMR exome

AF:

0.000183

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000859

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.000272

AC:

274

AN:

1007126

Hom.:

Cov.:

AF XY:

0.000264

AC XY:

AN XY:

302544

show subpopulations

Gnomad4 AFR exome

AF:

0.00834

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.000212

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000192

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000395

Gnomad4 OTH exome

AF:

0.000558

GnomAD4 genome

AF:

0.00179

AC:

200

AN:

112001

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

AN XY:

34183

show subpopulations

Gnomad4 AFR

AF:

0.00623

Gnomad4 AMR

AF:

0.000375

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00197

Alfa

AF:

0.00130

Hom.:

Bravo

AF:

0.00233

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jan 02, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.6

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00022

dbscSNV1_RF

Benign

0.060

SpliceAI score (max)

0.090

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