rs1557198365

chrX-154439090-G-AchrX-154439090-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_001493.3(GDI1):c.338G>A(p.Gly113Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000913 in 1,095,816 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes 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: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: GDI1 NM_001493.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.75

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, GDI1
• BP4: Computational evidence support a benign effect (MetaRNN=0.35244846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDI1	NM_001493.3	c.338G>A	p.Gly113Glu	missense_variant	4/11	ENST00000447750.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDI1	ENST00000447750.7	c.338G>A	p.Gly113Glu	missense_variant	4/11	1	NM_001493.3	P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.00000546 AC: 1 AN: 183119 Hom.: 0 AF XY: 0.0000148 AC XY: 1 AN XY: 67631

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: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.13e-7 AC: 1 AN: 1095816 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 1 AN XY: 361300

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: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 11, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
Cadd	Uncertain	24
Dann	Uncertain	0.99
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.50	T
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.93	D
Sift4G	Benign	0.16	T;T
Polyphen		0.054	.;B
Vest4		0.47
MutPred		0.40		Gain of ubiquitination at K112 (P = 0.0408);Gain of ubiquitination at K112 (P = 0.0408);
MVP		0.92
MPC		1.7
ClinPred		0.84	D
GERP RS		5.1
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.7
Varity_R		0.85
gMVP		0.82

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

Other links and lift over

dbSNP: rs1557198365; hg19: chrX-153667436;