rs185552165

chrX-154438512-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001493.3(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 NM_001493.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0002234
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.551

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]

ACMG classification

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 GnomAd at 52 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDI1	NM_001493.3	c.46-11C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000447750.7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00178 AC: 199 AN: 111949 Hom.: 0 Cov.: 23 AF XY: 0.00152 AC XY: 52 AN XY: 34121

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.: 0 AF XY: 0.000267 AC XY: 18 AN XY: 67418

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.: 1 Cov.: 22 AF XY: 0.000264 AC XY: 80 AN XY: 302544

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.: 0 Cov.: 23 AF XY: 0.00152 AC XY: 52 AN XY: 34183

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.: 6

Bravo AF: 0.00233

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Other links and lift over

dbSNP: rs185552165; hg19: chrX-153666858;