rs148818881

Variant names:

• chrX-154441180-G-T
• rs148818881
• NM_001493.3:c.804G>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001493.3(GDI1):​c.804G>T​(p.Val268Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000805 in 1,167,193 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 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 0.000018 (0 hom., 2 hem., cov: 24)
  • Exomes 𝑓: 0.000087 (0 hom. 26 hem.)
• Consequence: GDI1 NM_001493.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.163
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• intellectual disability, X-linked 41

  Inheritance: XL Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant X-154441180-G-T is Benign according to our data. Variant chrX-154441180-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 435313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.163 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.0000872 (92/1054898) while in subpopulation NFE AF = 0.000108 (87/802544). AF 95% confidence interval is 0.00009. There are 0 homozygotes in GnomAdExome4. There are 26 alleles in the male GnomAdExome4 subpopulation. Median coverage is 27. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 2 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001493.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDI1	NM_001493.3	MANE Select	c.804G>T	p.Val268Val	synonymous	Exon 7 of 11	NP_001484.1	A0A0S2Z3X8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDI1	ENST00000447750.7	TSL:1 MANE Select	c.804G>T	p.Val268Val	synonymous	Exon 7 of 11	ENSP00000394071.2	P31150
	GDI1	ENST00000468483.5	TSL:1	n.657G>T		non_coding_transcript_exon	Exon 1 of 4
	GDI1	ENST00000905223.1		c.804G>T	p.Val268Val	synonymous	Exon 7 of 11	ENSP00000575282.1

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112295 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000376

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000763 AC: 14 AN: 183400 AF XY: 0.0000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000872 AC: 92 AN: 1054898 Hom.: 0 Cov.: 27 AF XY: 0.0000800 AC XY: 26 AN XY: 325162

African (AFR) AF: 0.00 AC: 0 AN: 25634

American (AMR) AF: 0.0000853 AC: 3 AN: 35160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19148

East Asian (EAS) AF: 0.00 AC: 0 AN: 30044

South Asian (SAS) AF: 0.00 AC: 0 AN: 53133

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40489

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4018

European-Non Finnish (NFE) AF: 0.000108 AC: 87 AN: 802544

Other (OTH) AF: 0.0000447 AC: 2 AN: 44728

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112295 Hom.: 0 Cov.: 24 AF XY: 0.0000581 AC XY: 2 AN XY: 34435

African (AFR) AF: 0.00 AC: 0 AN: 30885

American (AMR) AF: 0.00 AC: 0 AN: 10688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3577

South Asian (SAS) AF: 0.00 AC: 0 AN: 2721

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6189

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53160

Other (OTH) AF: 0.00 AC: 0 AN: 1507

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.0000416

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	11
DANN	Benign	0.85
PhyloP100		0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs148818881; hg19: chrX-153669527;