X-154438805-C-G

Variant names:

• chrX-154438805-C-G
• rs1064796769
• NM_001493.3:c.194C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001493.3(GDI1):​c.194C>G​(p.Ser65Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,095,674 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: GDI1 NM_001493.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.36

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDI1	NM_001493.3	c.194C>G	p.Ser65Trp	missense_variant	Exon 3 of 11	ENST00000447750.7	NP_001484.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDI1	ENST00000447750.7	c.194C>G	p.Ser65Trp	missense_variant	Exon 3 of 11	1	NM_001493.3	ENSP00000394071.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.00000545 AC: 1 AN: 183498 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67932

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.13e-7 AC: 1 AN: 1095674 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 361110

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000284

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.91	.;D
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Pathogenic	0.64	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Uncertain	0.63	D
MutationAssessor	Uncertain	2.9	.;M
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.5	.;D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0030	.;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.99	.;D
Vest4		0.47
MutPred		0.33		Loss of disorder (P = 0.0034);Loss of disorder (P = 0.0034);
MVP		0.97
MPC		2.6
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.21
gMVP		0.93

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: rs1064796769; hg19: chrX-153667151;