rs1557198307

Variant names:

• chrX-154438804-T-A
• rs1557198307
• NM_001493.3:c.193T>A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP6

The NM_001493.3(GDI1):​c.193T>A​(p.Ser65Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: GDI1 NM_001493.3 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 1.42

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11152628).
• BP6: Variant X-154438804-T-A is Benign according to our data. Variant chrX-154438804-T-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 435315.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDI1	NM_001493.3	c.193T>A	p.Ser65Thr	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.193T>A	p.Ser65Thr	missense_variant	Exon 3 of 11	1	NM_001493.3	ENSP00000394071.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Sep 07, 2016

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Intellectual disability, X-linked 41;C4310819:Immunodeficiency 47 Benign:1

Sep 20, 2024

3billion, Medical Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The hemizygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the hemizygous variant. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.90
DEOGEN2	Uncertain	0.54	.;D
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.76	T;T
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.8	.;L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.92	.;N
REVEL	Benign	0.11
Sift	Benign	0.31	.;T
Sift4G	Benign	0.28	T;T
Polyphen		0.0060	.;B
Vest4		0.067
MutPred		0.28		Loss of disorder (P = 0.0915);Loss of disorder (P = 0.0915);
MVP		0.81
MPC		1.1
ClinPred		0.10	T
GERP RS		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.093
gMVP		0.81

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: rs1557198307; hg19: chrX-153667150;